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Article

Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway

  • Authors:
    • Zijun Lai
    • Zhaokun Yan
    • Wujin Chen
    • Jun Peng
    • Jianyu Feng
    • Qiongyu Li
    • Yiyi Jin
    • Jiumao Lin
  • View Affiliations / Copyright

    Affiliations: Academy of Integrative Medicine, Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China, Oncology Department of The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350004, P.R. China
  • Pages: 7752-7758
    |
    Published online on: September 18, 2017
       https://doi.org/10.3892/mmr.2017.7500
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Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract, and threatens the survival and health of patients with CRC. Chemotherapy remains one of the main therapeutic approaches for patients with CRC; however, drug resistance limits the long‑term use. CRC cells with multi‑drug resistance (MDR) exhibit increased survival times and metastatic potential, which may lead to the recurrence and metastasis of CRC. In addition, MDR is one of the major causes of chemotherapy failure in clinical treatment. Hedyotis diffusa Willd (HDW) has been used in the treatment of inflammation‑associated diseases and malignant tumors, including CRC. The authors previously demonstrated that HDW could reverse MDR in CRC cells; however, its underlying mechanism, particularly in MDR‑associated metastasis, remains to be elucidated. In the present study, the drug‑resistant CRC cell line HCT‑8/5‑fluorouracil (5‑FU) was used to investigate the effect of HDW on the growth and metastasis of cancer cells. Cell viability was assessed using the MTT assay. Cell adhesion potential was evaluated using adhesion experiments. Cell migration was assessed using wound healing and Transwell assays. The mRNA and protein expression levels of crucial factors in the transforming growth factor‑β (TGF‑β) signaling pathway, including TGF‑β, Mothers against decapentaplegic homolog 4 (SMAD4), neural (N)‑cadherin, and epithelial (E)‑cadherin, were analyzed using the reverse transcription‑semi‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that the HCT‑8/5‑FU cell line was more resistant to 5‑FU and thus can be used as the resistant cell model. HDW was able to inhibit the viability, and adhesive, migratory and invasion potential of the HCT‑8/5‑FU cells. In addition, HDW was able to downregulate the expression of TGF‑β, SMAD4 and N‑cadherin, and upregulate E‑cadherin, at the gene and protein level. In conclusion, the results demonstrated that HDW may suppress the metastasis of 5‑FU‑resistant CRC cells via regulation of the TGF‑β signaling pathway, which was also considered to be one of the underlying mechanisms of its anti‑CRC effect.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B and Starling N: Colorectal cancer. Lancet. 375:1030–1047. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Jiang WQ, Fu FF, Li YX, Wang WB, Wang HH, Jiang HP and Teng LS: Molecular biomarkers of colorectal cancer: Prognostic and predictive tools for clinical practice. J Zhejiang Univ Sci B. 13:663–675. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Aakif M, Balfe P, Elfaedy O, Awan FN, Pretorius F, Silvio L, Castinera C and Mustafa H: Study on colorectal cancer presentation, treatment and follow-up. Int J Colorectal Dis. 31:1361–1363. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Du B and Shim JS: Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer. Molecules. 21(pii): E9652016. View Article : Google Scholar : PubMed/NCBI

6 

Phillips TA, Howell A, Grieve RJ and Welling PG: Pharmacokinetics of oral and intravenous fluorouracil in humans. J Pharm Sci. 69:1428–1431. 1980. View Article : Google Scholar : PubMed/NCBI

7 

Juchum M, Günther M and Laufer SA: Fighting cancer drug resistance: Opportunities and challenges for mutation-specific EGFR inhibitors. Drug Resist Update. 20:12–28. 2015. View Article : Google Scholar

8 

Kim JK, Kang KA, Piao MJ, Ryu YS, Han X, Fernando PM, Oh MC, Park JE, Shilnikova K, Boo SJ, et al: Endoplasmic reticulum stress induces 5-fluorouracil resistance in human colon cancer cells. Environ Toxicol Pharmacol. 44:128–133. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Shen A, Chen H, Chen Y, Lin J, Lin W, Liu L, Sferra TJ and Peng J: Pien Tze Huang overcomes multidrug resistance and epithelial-mesenchymal transition in human colorectal carcinoma cells via suppression of TGF-β pathway. Evid Based Complement Alternat Med. 2014:6794362014. View Article : Google Scholar : PubMed/NCBI

10 

Pecina-Slaus N, Cicvara-Pecina T and Kafka A: Epithelial-to-mesenchymal transition: Possible role in meningiomas. Front Biosci (Elite Ed). 4:889–896. 2012.PubMed/NCBI

11 

Guarino M, Rubino B and Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 39:305–318. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Roberts AB: Molecular and cell biology of TGF-beta. Miner Electrolyte Metab. 24:111–119. 1998. View Article : Google Scholar : PubMed/NCBI

13 

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 : PubMed/NCBI

14 

Trapani JA: The dual adverse effects of TGF-beta secretion on tumor progression. Cancer Cell. 8:349–350. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Heldin CH, Vanlandewijck M and Moustakas A: Regulation of EMT by TGFβ in cancer. FEBS Lett. 586:1959–1970. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Massagué J: TGFbeta in cancer. Cell. 134:215–230. 2008. View Article : Google Scholar : PubMed/NCBI

17 

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 : PubMed/NCBI

18 

Brunen D, Willems SM, Kellner U, Midgley R, Simon I and Bernards R: TGF-β: An emerging player in drug resistance. Cell Cycle. 12:2960–2968. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Moustakas A and Heldin P: TGFβ and matrix-regulated epithelial to mesenchymal transition. Biochim Biophys Acta. 1840:2621–2634. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Song LR: Zhonghuabencao. Shanghai Science and Technology Press; Shanghai: pp. 4331999

21 

Yang JJ, Hsu HY, Ho YH and Lin CC: Comparative study on the immunocompetent activity of three different kinds of Peh-Hue-Juwa-Chi-Cao, Hedyotis diffusa, H. corymbosa and Mollugo pentaphylla after sublethal whole body x-irradiation. Phytother Res. 11:428–432. 1997. View Article : Google Scholar

22 

Li R, Zhao HR and Lin YM: Anti-tumor effect and protective effect on chemotherapeutic damage of water soluble extracts from Hedyotis diffusa. J Chin Pharmaceu Sci. 11:54–58. 2002.

23 

Cai Q, Lin J, Wei L, Zhang L, Wang L, Zhan Y, Zeng J, Xu W, Shen A, Hong Z and Peng J: Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of STAT3 signaling pathway. Int J Mol Sci. 13:6117–6128. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Lin J, Wei L, Shen A, Cai Q, Xu W, Li H, Zhan Y, Hong Z and Peng J: Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis. Int J Oncol. 42:651–656. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Lin J, Chen Y, Wei L, Chen X, Xu W, Hong Z, Sferra TJ and Peng J: Hedyotis diffusa Willd extract induces apoptosis via activation of the mitochondrion-dependent pathway in human colon carcinoma cells. Int J Oncol. 37:1331–1338. 2010.PubMed/NCBI

26 

Lin J, Wei L, Xu W, Hong Z, Liu X and Peng J: Effect of Hedyotis diffusa Willd extract on tumor angiogenesis. Mol Med Rep. 4:1283–1288. 2011.PubMed/NCBI

27 

Lin M, Lin J, Wei L, Xu W, Hong Z, Cai Q, Peng J and Zhu D: Hedyotis diffusa Willd extract inhibits HT-29 cell proliferation via cell cycle arrest. Exp Ther Med. 4:307–310. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Li Q, Wang X, Shen A, Zhang Y, Chen Y, Sferra T, Lin J and Peng J: Hedyotis diffusa Willd overcomes 5-fluorouracil resistance in human colorectal cancer HCT-8/5-FU cells by downregulating the expression of P-glycoprotein and ATP-binding casette subfamily G member 2. Exp Ther Med. 10:1845–1850. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Valastyan S and Weinberg RA: Tumor metastasis: Molecular insights and evolving paradigms. Cell. 147:275–292. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Moustakas A and Heldin CH: The regulation of TGFbeta signal transduction. Development. 136:3699–3714. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Nieto MA: Epithelial plasticity: A common theme in embryonic and cancer cells. Science. 342:12348502013. View Article : Google Scholar : PubMed/NCBI

32 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Shi Y and Massagué J: Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113:685–700. 2003. View Article : Google Scholar : PubMed/NCBI

34 

Zi Z, Chapnick DA and Liu X: Dynamics of TGF-β/SMAD signaling. FEBS Lett. 586:1921–1928. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Massagué J: How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 1:169–178. 2000. View Article : Google Scholar : PubMed/NCBI

36 

Massagué J and Wotton D: Transcriptional control by the TGF-beta/Smad signaling system. EMBO J. 19:1745–1754. 2000. View Article : Google Scholar : PubMed/NCBI

37 

Batlle E, Sancho E, Francí C, Domínguez D, Monfar M, Baulida J and García De Herreros A: The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2:84–89. 2000. View Article : Google Scholar : PubMed/NCBI

38 

Lamouille S, Xu J and Derynck R: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 15:178–196. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Tanaka T, Goto K and Iino M: Sec8 modulates TGF-β induced EMT by controlling N-cadherin via regulation of Smad3/4. Cell Signal. 29:115–126. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lai Z, Yan Z, Chen W, Peng J, Feng J, Li Q, Jin Y and Lin J: Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway. Mol Med Rep 16: 7752-7758, 2017.
APA
Lai, Z., Yan, Z., Chen, W., Peng, J., Feng, J., Li, Q. ... Lin, J. (2017). Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway. Molecular Medicine Reports, 16, 7752-7758. https://doi.org/10.3892/mmr.2017.7500
MLA
Lai, Z., Yan, Z., Chen, W., Peng, J., Feng, J., Li, Q., Jin, Y., Lin, J."Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 16.5 (2017): 7752-7758.
Chicago
Lai, Z., Yan, Z., Chen, W., Peng, J., Feng, J., Li, Q., Jin, Y., Lin, J."Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 16, no. 5 (2017): 7752-7758. https://doi.org/10.3892/mmr.2017.7500
Copy and paste a formatted citation
x
Spandidos Publications style
Lai Z, Yan Z, Chen W, Peng J, Feng J, Li Q, Jin Y and Lin J: Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway. Mol Med Rep 16: 7752-7758, 2017.
APA
Lai, Z., Yan, Z., Chen, W., Peng, J., Feng, J., Li, Q. ... Lin, J. (2017). Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway. Molecular Medicine Reports, 16, 7752-7758. https://doi.org/10.3892/mmr.2017.7500
MLA
Lai, Z., Yan, Z., Chen, W., Peng, J., Feng, J., Li, Q., Jin, Y., Lin, J."Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 16.5 (2017): 7752-7758.
Chicago
Lai, Z., Yan, Z., Chen, W., Peng, J., Feng, J., Li, Q., Jin, Y., Lin, J."Hedyotis diffusa Willd suppresses metastasis in 5‑fluorouracil‑resistant colorectal cancer cells by regulating the TGF‑β signaling pathway". Molecular Medicine Reports 16, no. 5 (2017): 7752-7758. https://doi.org/10.3892/mmr.2017.7500
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