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TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway

  • Authors:
    • Dengwei He
    • Jiawei Gao
    • Lin Zheng
    • Shijie Liu
    • Lin Ye
    • Hehuan Lai
    • Bin Pan
    • Wenzheng Pan
    • Chao Lou
    • Zhenzhong Chen
    • Shunwu Fan
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, P.R. China, Department of Orthopedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 84
    |
    Published online on: September 16, 2021
       https://doi.org/10.3892/ijo.2021.5264
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Abstract

Osteosarcoma (OS) is the most common malignant bone tumor and the long‑term survival rates remain unsatisfactory. Transforming growth factor‑β (TGF‑β) has been revealed to play a crucial role in OS progression, and RepSox is an effective TGF‑β inhibitor. In the present study, the effect of RepSox on the proliferation of the OS cell lines (HOS and 143B) was detected. The results revealed that RepSox effectively inhibited the proliferation of OS cells by inducing S‑phase arrest and apoptosis. Moreover, the inhibitory effect of RepSox on cell migration and invasion was confirmed by wound‑healing and Transwell assays. Furthermore, western blotting revealed that the protein levels of molecules associated with the epithelial‑mesenchymal transition (EMT) phenotype, including E‑cadherin, N‑cadherin, Vimentin, matrix metalloproteinase (MMP)‑2 and MMP‑9, were reduced by RepSox treatment. Concurrently, it was also revealed that the JNK and Smad3 signaling pathway was inhibited. Our in vivo findings using a xenograft model also revealed that RepSox markedly inhibited the growth of tumors. In general, our data demonstrated that RepSox suppressed OS proliferation, EMT and promoted apoptosis by inhibiting the JNK/Smad3 signaling pathway. Thus, RepSox may be a potential anti‑OS drug.
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View References

1 

Friedrich P, Ortiz R, Strait K, Fuentes S, Gamboa Y, Arambú I, Ah-Chu-Sanchez M, London W, Rodríguez-Galindo C, Antillón-Klussmann F, et al: Central American Association of Pediatric Hematologists Oncologists AHOPCA: Pediatric sarcoma in Central America: Outcomes, challenges, and plans for improvement. Cancer. 119:871–879. 2013. View Article : Google Scholar

2 

Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar

3 

Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A and Picci P: Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 106:1154–1161. 2006. View Article : Google Scholar

4 

Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, et al: Prognostic factors in high-grade osteosarcoma of the extremities or trunk: An analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol. 20:776–790. 2002. View Article : Google Scholar

5 

Derynck R and Zhang YE: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar

6 

Zhang YE: Non-Smad signaling pathways of the TGF-β family. Cold Spring Harb Perspect Biol. 9:92017. View Article : Google Scholar

7 

Batlle E and Massagué J: Transforming growth factor-β signaling in immunity and cancer. Immunity. 50:924–940. 2019. View Article : Google Scholar

8 

Walker RA and Dearing SJ: Transforming growth factor beta 1 in ductal carcinoma in situ and invasive carcinomas of the breast. Eur J Cancer. 28:641–644. 1992. View Article : Google Scholar

9 

Adekoya TO and Richardson RM: Cytokines and chemokines as mediators of prostate cancer metastasis. Int J Mol Sci. 21:212020. View Article : Google Scholar

10 

Stolfi C, Troncone E, Marafini I and Monteleone G: Role of TGF-beta and Smad7 in gut inflammation, fibrosis and cancer. Biomolecules. 11:112020. View Article : Google Scholar

11 

Xu S, Yang S, Sun G, Huang W and Zhang Y: Transforming growth factor-beta polymorphisms and serum level in the development of osteosarcoma. DNA Cell Biol. 33:802–806. 2014. View Article : Google Scholar

12 

Lamora A, Talbot J, Bougras G, Amiaud J, Leduc M, Chesneau J, Taurelle J, Stresing V, Le Deley MC, Heymann MF, et al: Overexpression of smad7 blocks primary tumor growth and lung metastasis development in osteosarcoma. Clin Cancer Res. 20:5097–5112. 2014. View Article : Google Scholar

13 

Gellibert F, Woolven J, Fouchet MH, Mathews N, Goodland H, Lovegrove V, Laroze A, Nguyen VL, Sautet S, Wang R, et al: Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. J Med Chem. 47:4494–4506. 2004. View Article : Google Scholar

14 

Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, et al: A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell. 5:491–503. 2009. View Article : Google Scholar

15 

Mei L, Sang W, Chen Z, Zheng L, Jin K, Lou C, Huang W and He D: Small molecule inhibitor RepSox prevented ovariectomy-induced osteoporosis by suppressing osteoclast differentiation and bone resorption. J Cell Physiol. 233:9724–9738. 2018. View Article : Google Scholar

16 

Fu Y, Huang C, Xu X, Gu H, Ye Y, Jiang C, Qiu Z and Xie X: Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails. Cell Res. 25:1013–1024. 2015. View Article : Google Scholar

17 

Jajosky AN, Coad JE, Vos JA, Martin KH, Senft JR, Wenger SL and Gibson LF: RepSox slows decay of CD34+ acute myeloid leukemia cells and decreases T cell immunoglobulin mucin-3 expression. Stem Cells Transl Med. 3:836–848. 2014. View Article : Google Scholar

18 

Ide M, Jinnin M, Tomizawa Y, Wang Z, Kajihara I, Fukushima S, Hashizume Y, Asano Y and Ihn H: Transforming growth factor β-inhibitor Repsox downregulates collagen expression of scleroderma dermal fibroblasts and prevents bleomycin-induced mice skin fibrosis. Exp Dermatol. 26:1139–1143. 2017. View Article : Google Scholar

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

20 

Jiang X, Shan J, Dai N, Zhong Z, Qing Y, Yang Y, Zhang S, Li C, Sui J, Ren T, et al: Apurinic/apyrimidinic endonuclease 1 regulates angiogenesis in a transforming growth factor β-dependent manner in human osteosarcoma. Cancer Sci. 106:1394–1401. 2015. View Article : Google Scholar

21 

Lu KH, Su SC, Lin CW, Hsieh YH, Lin YC, Chien MH, Reiter RJ and Yang SF: Melatonin attenuates osteosarcoma cell invasion by suppression of C-C motif chemokine ligand 24 through inhibition of the c-Jun N-terminal kinase pathway. J Pineal Res. 65:e125072018. View Article : Google Scholar

22 

Sun Y, Xia P, Zhang H, Liu B and Shi Y: P53 is required for Doxorubicin-induced apoptosis via the TGF-beta signaling pathway in osteosarcoma-derived cells. Am J Cancer Res. 6:114–125. 2015.

23 

Wang H, Zhang T, Sun W, Wang Z, Zuo D, Zhou Z, Li S, Xu J, Yin F, Hua Y, et al: Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo. Cell Death Dis. 7:e22472016. View Article : Google Scholar

24 

Wang S, Li H, Chen S, Wang Z, Yao Y, Chen T, Ye Z and Lin P: Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway. Int J Oncol. 56:1417–1428. 2020.

25 

Wang Y, Deng X, Yu C, Zhao G, Zhou J, Zhang G, Li M, Jiang D, Quan Z and Zhang Y: Synergistic inhibitory effects of capsaicin combined with cisplatin on human osteosarcoma in culture and in xenografts. J Exp Clin Cancer Res. 37:2512018. View Article : Google Scholar

26 

Jie Z, Xie Z, Zhao X, Sun X, Yu H, Pan X, Shen S, Qin A, Fang X and Fan S: Glabridin inhibits osteosarcoma migration and invasion via blocking the p38- and JNK-mediated CREB-AP1 complexes formation. J Cell Physiol. 234:4167–4178. 2019. View Article : Google Scholar

27 

Lin RC, Yang SF, Chiou HL, Hsieh SC, Wen SH, Lu KH and Hsieh YH: Licochalcone A-induced apoptosis through the activation of p38MAPK pathway mediated mitochondrial pathways of apoptosis in human osteosarcoma cells in vitro and in vivo. Cells. 8:82019. View Article : Google Scholar

28 

Lu KH, Chen PN, Hsieh YH, Lin CY, Cheng FY, Chiu PC, Chu SC and Hsieh YS: 3-Hydroxyflavone inhibits human osteosarcoma U2OS and 143B cells metastasis by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and reduces 143B tumor growth in vivo. Food Chem Toxicol. 97:177–186. 2016. View Article : Google Scholar

29 

Goorin AM, Harris MB, Bernstein M, Ferguson W, Devidas M, Siegal GP, Gebhardt MC, Schwartz CL, Link M and Grier HE: Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: A pediatric oncology group trial. J Clin Oncol. 20:426–433. 2002. View Article : Google Scholar

30 

Kempf-Bielack B, Bielack SS, Jürgens H, Branscheid D, Berdel WE, Exner GU, Göbel U, Helmke K, Jundt G, Kabisch H, et al: Osteosarcoma relapse after combined modality therapy: An analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 23:559–568. 2005. View Article : Google Scholar

31 

Bierie B and Moses HL: Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 6:506–520. 2006. View Article : Google Scholar

32 

Friedman E, Gold LI, Klimstra D, Zeng ZS, Winawer S and Cohen A: High levels of transforming growth factor beta 1 correlate with disease progression in human colon cancer. Cancer Epidemiol Biomarkers Prev. 4:549–554. 1995.

33 

Wikström P, Stattin P, Franck-Lissbrant I, Damber JE and Bergh A: Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Prostate. 37:19–29. 1998. View Article : Google Scholar

34 

Roberts AB and Wakefield LM: The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA. 100:8621–8623. 2003. View Article : Google Scholar

35 

Derynck R, Akhurst RJ and Balmain A: TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 29:117–129. 2001. View Article : Google Scholar

36 

Costanza B, Umelo IA, Bellier J, Castronovo V and Turtoi A: Stromal modulators of TGF-β in cancer. J Clin Med. 6:62017. View Article : Google Scholar

37 

Matsuyama S, Iwadate M, Kondo M, Saitoh M, Hanyu A, Shimizu K, Aburatani H, Mishima HK, Imamura T, Miyazono K, et al: SB-431542 and Gleevec inhibit transforming growth factor-beta-induced proliferation of human osteosarcoma cells. Cancer Res. 63:7791–7798. 2003.

38 

Franchi A, Arganini L, Baroni G, Calzolari A, Capanna R, Campanacci D, Caldora P, Masi L, Brandi ML and Zampi G: Expression of transforming growth factor beta isoforms in osteosarcoma variants: Association of TGF beta 1 with high-grade osteosarcomas. J Pathol. 185:284–289. 1998. View Article : Google Scholar

39 

Mohseny AB, Cai Y, Kuijjer M, Xiao W, van den Akker B, de Andrea CE, Jacobs R, ten Dijke P, Hogendoorn PC and Cleton-Jansen AM: The activities of Smad and Gli mediated signalling pathways in high-grade conventional osteosarcoma. Eur J Cancer. 48:3429–3438. 2012. View Article : Google Scholar

40 

Jang CW, Chen CH, Chen CC, Chen JY, Su YH and Chen RH: TGF-beta induces apoptosis through Smad-mediated expression of DAP-kinase. Nat Cell Biol. 4:51–58. 2002. View Article : Google Scholar

41 

Hannon GJ and Beach D: p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature. 371:257–261. 1994. View Article : Google Scholar

42 

Reynisdóttir I, Polyak K, Iavarone A and Massagué J: Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev. 9:1831–1845. 1995. View Article : Google Scholar

43 

Ghelli Luserna di Rora'AIacobucci I and Martinelli G: The cell cycle checkpoint inhibitors in the treatment of leukemias. J Hematol Oncol. 10:772017. View Article : Google Scholar

44 

Wang JL, Quan Q, Ji R, Guo XY, Zhang JM, Li X and Liu YG: Isorhamnetin suppresses PANC-1 pancreatic cancer cell proliferation through S phase arrest. Biomed Pharmacother. 108:925–933. 2018. View Article : Google Scholar

45 

Szmyd R, Niska-Blakie J, Diril MK, Renck Nunes P, Tzelepis K, Lacroix A, van Hul N, Deng LW, Matos J, Dreesen O, et al: Premature activation of Cdk1 leads to mitotic events in S phase and embryonic lethality. Oncogene. 38:998–1018. 2019. View Article : Google Scholar

46 

Koff A, Giordano A, Desai D, Yamashita K, Harper JW, Elledge S, Nishimoto T, Morgan DO, Franza BR and Roberts JM: Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science. 257:1689–1694. 1992. View Article : Google Scholar

47 

Girard F, Strausfeld U, Fernandez A and Lamb NJ: Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. Cell. 67:1169–1179. 1991. View Article : Google Scholar

48 

Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R and Beach D: p21 is a universal inhibitor of cyclin kinases. Nature. 366:701–704. 1993. View Article : Google Scholar

49 

Yeh HW, Lee SS, Chang CY, Lang YD and Jou YS: A new switch for TGFβ in cancer. Cancer Res. 79:3797–3805. 2019. View Article : Google Scholar

50 

Massagué J: TGFbeta in Cancer. Cell. 134:215–230. 2008. View Article : Google Scholar

51 

Morrison CD, Parvani JG and Schiemann WP: The relevance of the TGF-β Paradox to EMT-MET programs. Cancer Lett. 341:30–40. 2013. View Article : Google Scholar

52 

Yu X, Yustein JT and Xu J: Research models and mesenchymal/epithelial plasticity of osteosarcoma. Cell Biosci. 11:942021. View Article : Google Scholar

53 

Yang G, Yuan J and Li K: EMT transcription factors: Implication in osteosarcoma. Med Oncol. 30:6972013. View Article : Google Scholar

54 

Sharili AS, Allen S, Smith K, Hargreaves J, Price J and McGonnell I: Expression of Snail2 in long bone osteosarcomas correlates with tumour malignancy. Tumour Biol. 32:515–526. 2011. View Article : Google Scholar

55 

Wensman H, Göransson H, Leuchowius KJ, Strömberg S, Pontén F, Isaksson A, Rutteman GR, Heldin NE, Pejler G and Hellmén E: Extensive expression of craniofacial related homeobox genes in canine mammary sarcomas. Breast Cancer Res Treat. 118:333–343. 2009. View Article : Google Scholar

56 

Wu J, Liao Q, He H, Zhong D and Yin K: TWIST interacts with β-catenin signaling on osteosarcoma cell survival against cisplatin. Mol Carcinog. 53:440–446. 2014. View Article : Google Scholar

57 

Chen J, Song Y, Yang J, Gong L, Zhao P, Zhang Y and Su H: The up-regulation of cysteine-rich protein 61 induced by transforming growth factor beta enhances osteosarcoma cell migration. Mol Cell Biochem. 384:269–277. 2013. View Article : Google Scholar

58 

Huang Y, Yang Y, Gao R, Yang X, Yan X, Wang C, Jiang S and Yu L: RLIM interacts with Smurf2 and promotes TGF-β induced U2OS cell migration. Biochem Biophys Res Commun. 414:181–185. 2011. View Article : Google Scholar

59 

Kunita A, Kashima TG, Ohazama A, Grigoriadis AE and Fukayama M: Podoplanin is regulated by AP-1 and promotes platelet aggregation and cell migration in osteosarcoma. Am J Pathol. 179:1041–1049. 2011. View Article : Google Scholar

60 

Sung JY, Park SY, Kim JH, Kang HG, Yoon JH, Na YS, Kim YN and Park BK: Interferon consensus sequence-binding protein (ICSBP) promotes epithelial-to-mesenchymal transition (EMT)-like phenomena, cell-motility, and invasion via TGF-β signaling in U2OS cells. Cell Death Dis. 5:e12242014. View Article : Google Scholar

61 

Borok Z: Role for alpha3 integrin in EMT and pulmonary fibrosis. J Clin Invest. 119:7–10. 2009.

62 

Javelaud D and Mauviel A: Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-beta: Implications for carcinogenesis. Oncogene. 24:5742–5750. 2005. View Article : Google Scholar

63 

Chueh FS, Chen YY, Huang AC, Ho HC, Liao CL, Yang JS, Kuo CL and Chung JG: Bufalin-inhibited migration and invasion in human osteosarcoma U-2 OS cells is carried out by suppression of the matrix metalloproteinase-2, ERK, and JNK signaling pathways. Environ Toxicol. 29:21–29. 2014. View Article : Google Scholar

64 

Fromigué O, Hamidouche Z and Marie PJ: Blockade of the RhoA-JNK-c-Jun-MMP2 cascade by atorvastatin reduces osteosarcoma cell invasion. J Biol Chem. 283:30549–30556. 2008. View Article : Google Scholar

65 

Jung O and Lee SY: Synergistic anticancer effects of timosaponin AIII and ginsenosides in MG63 human osteosarcoma cells. J Ginseng Res. 43:488–495. 2019. View Article : Google Scholar

66 

Liao CL, Lai KC, Huang AC, Yang JS, Lin JJ, Wu SH, Gibson Wood W, Lin JG and Chung JG: Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and PKC signaling pathways. Food Chem Toxicol. 50:1734–1740. 2012. View Article : Google Scholar

67 

Lamora A, Mullard M, Amiaud J, Brion R, Heymann D, Redini F and Verrecchia F: Anticancer activity of halofuginone in a preclinical model of osteosarcoma: Inhibition of tumor growth and lung metastases. Oncotarget. 6:14413–14427. 2015. View Article : Google Scholar

68 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar

69 

Nishihira J, Ishibashi T, Fukushima T, Sun B, Sato Y and Todo S: Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis. Ann NY Acad Sci. 995:171–182. 2003. View Article : Google Scholar

70 

Ogawa H, Nishihira J, Sato Y, Kondo M, Takahashi N, Oshima T and Todo S: An antibody for macrophage migration inhibitory factor suppresses tumour growth and inhibits tumour-associated angiogenesis. Cytokine. 12:309–314. 2000. View Article : Google Scholar

71 

Yaddanapudi K, Putty K, Rendon BE, Lamont GJ, Faughn JD, Satoskar A, Lasnik A, Eaton JW and Mitchell RA: Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor. J Immunol. 190:2984–2993. 2013. View Article : Google Scholar

72 

Li Y, Li X, Lu Y, Chaurasiya B, Mi G, Shi D, Chen D, Webster TJ, Tu J and Shen Y: Co-delivery of Poria cocos extract and doxorubicin as an 'all-in-one' nanocarrier to combat breast cancer multidrug resistance during chemotherapy. Nanomedicine. 23:1020952020. View Article : Google Scholar

73 

Xu J, Wang H, Hu Y, Zhang YS, Wen L, Yin F, Wang Z, Zhang Y, Li S, Miao Y, et al: Inhibition of CaMKIIα activity enhances antitumor effect of fullerene C60 nanocrystals by suppression of autophagic degradation. Adv Sci (Weinh). 6:18012332019. View Article : Google Scholar

74 

Zhang Y, Wang F, Li M, Yu Z, Qi R, Ding J, Zhang Z and Chen X: Self-stabilized hyaluronate nanogel for intracellular codelivery of doxorubicin and cisplatin to osteosarcoma. Adv Sci (Weinh). 5:17008212018. View Article : Google Scholar

75 

Li D, Xu W, Li P, Ding J, Cheng Z, Chen L, Yan L and Chen X: Self-targeted polysaccharide prodrug suppresses orthotopic hepatoma. Mol Pharm. 13:4231–4235. 2016. View Article : Google Scholar

76 

Wang J, Li Z, Wang Z, Yu Y, Li D, Li B and Ding J: Nanomaterials for combinational radio-immuno oncotherapy. Adv Funct Mater. 30:19106762020. View Article : Google Scholar

77 

Zhao D, Zhu T, Li J, Cui L, Zhang Z, Zhuang X and Ding J: Poly(lactic-co-glycolic acid)-based composite bone-substitute materials. Bioact Mater. 6:346–360. 2020. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
He D, Gao J, Zheng L, Liu S, Ye L, Lai H, Pan B, Pan W, Lou C, Chen Z, Chen Z, et al: TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway. Int J Oncol 59: 84, 2021.
APA
He, D., Gao, J., Zheng, L., Liu, S., Ye, L., Lai, H. ... Fan, S. (2021). TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway. International Journal of Oncology, 59, 84. https://doi.org/10.3892/ijo.2021.5264
MLA
He, D., Gao, J., Zheng, L., Liu, S., Ye, L., Lai, H., Pan, B., Pan, W., Lou, C., Chen, Z., Fan, S."TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway". International Journal of Oncology 59.5 (2021): 84.
Chicago
He, D., Gao, J., Zheng, L., Liu, S., Ye, L., Lai, H., Pan, B., Pan, W., Lou, C., Chen, Z., Fan, S."TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway". International Journal of Oncology 59, no. 5 (2021): 84. https://doi.org/10.3892/ijo.2021.5264
Copy and paste a formatted citation
x
Spandidos Publications style
He D, Gao J, Zheng L, Liu S, Ye L, Lai H, Pan B, Pan W, Lou C, Chen Z, Chen Z, et al: TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway. Int J Oncol 59: 84, 2021.
APA
He, D., Gao, J., Zheng, L., Liu, S., Ye, L., Lai, H. ... Fan, S. (2021). TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway. International Journal of Oncology, 59, 84. https://doi.org/10.3892/ijo.2021.5264
MLA
He, D., Gao, J., Zheng, L., Liu, S., Ye, L., Lai, H., Pan, B., Pan, W., Lou, C., Chen, Z., Fan, S."TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway". International Journal of Oncology 59.5 (2021): 84.
Chicago
He, D., Gao, J., Zheng, L., Liu, S., Ye, L., Lai, H., Pan, B., Pan, W., Lou, C., Chen, Z., Fan, S."TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway". International Journal of Oncology 59, no. 5 (2021): 84. https://doi.org/10.3892/ijo.2021.5264
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