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International Journal of Molecular Medicine
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September-2024 Volume 54 Issue 3

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Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma

  • Authors:
    • Zhenzhen Yang
    • Hongtao Liu
    • Yinsen Song
    • Na Gao
    • Pan Gao
    • Yiran Hui
    • Yueheng Li
    • Tianli Fan
  • View Affiliations / Copyright

    Affiliations: The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan 450003, P.R. China, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 77
    |
    Published online on: July 10, 2024
       https://doi.org/10.3892/ijmm.2024.5401
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Abstract

Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem‑like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti‑tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)‑resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit‑8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT‑related proteins and stem cell markers after sphere formation. Parental cells and drug‑resistant cells were screened by high‑throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX‑resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug‑resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX‑resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX‑resistant ESCC and could be a promising agent for the treatment of PTX‑resistant ESCC cancers.
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View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Zhang Y: Epidemiology of esophageal cancer. World J Gastroenterol. 19:5598–5606. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Abnet CC, Arnold M and Wei WQ: Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 154:360–373. 2018. View Article : Google Scholar

4 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Lin Y, Totsuka Y, He Y, Kikuchi S, Qiao Y, Ueda J, Wei W, Inoue M and Tanaka H: Epidemiology of esophageal cancer in Japan and China. J Epidemiol. 23:233–242. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Hiripi E, Jansen L, Gondos A, Emrich K, Holleczek B, Katalinic A, Luttmann S, Nennecke A and Brenner H; Gekid Cancer Survival Working Group: Survival of stomach and esophagus cancer patients in Germany in the early 21st century. Acta Oncol. 51:906–914. 2012. View Article : Google Scholar : PubMed/NCBI

7 

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, et al: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 366:2074–2084. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J and Simes J; Australasian Gastro-Intestinal Trials Group: Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: A meta-analysis. Lancet Oncol. 8:226–234. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A, et al: A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 19:68–74. 2012. View Article : Google Scholar

10 

Liu Y, Ren Z, Yuan L, Xu S, Yao Z, Qiao L and Li K: Paclitaxel plus cisplatin vs. 5-fluorouracil plus cisplatin as first-line treatment for patients with advanced squamous cell esophageal cancer. Am J Cancer Res. 6:2345–2350. 2016.PubMed/NCBI

11 

Hummel R, Sie C, Watson DI, Wang T, Ansar A, Michael MZ, Van der Hoek M, Haier J and Hussey DJ: MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines. World J Gastroenterol. 20:14904–1412. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Limtrakul P, Anuchapreeda S and Buddhasukh D: Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids. BMC Cancer. 4:132004. View Article : Google Scholar : PubMed/NCBI

13 

Lopez-Lazaro M: Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem. 9:31–59. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Shi R, Huang Q, Zhu X, Ong YB, Zhao B, Lu J, Ong CN and Shen HM: Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase-mediated p53 phosphorylation and stabilization. Mol Cancer Ther. 6:1338–1347. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Chian S, Li YY, Wang XJ and Tang XW: Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway. Asian Pac J Cancer Prev. 15:2911–2916. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Pandurangan AK, Dharmalingam P, Sadagopan SK and Ganapasam S: Luteolin inhibits matrix metalloproteinase 9 and 2 in azoxymethane-induced colon carcinogenesis. Hum Exp Toxicol. 33:1176–1185. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Carsten VF and Cardinale PJ: The overdenture-a review. N Y State Dent J. 44:331–334. 1978.PubMed/NCBI

18 

Wu YT, Chen L, Tan ZB, Fan HJ, Xie LP, Zhang WT, Chen HM, Li J, Liu B and Zhou YC: Luteolin inhibits vascular smooth muscle cell proliferation and migration by inhibiting TGFBR1 signaling. Front Pharmacol. 9:10592018. View Article : Google Scholar : PubMed/NCBI

19 

Tsai KJ, Tsai HY, Tsai CC, Chen TY, Hsieh TH, Chen CL, Mbuyisa L, Huang YB and Lin MW: Luteolin inhibits breast cancer stemness and enhances chemosensitivity through the Nrf2-mediated pathway. Molecules. 26:64522021. View Article : Google Scholar : PubMed/NCBI

20 

Ma J, Chen X, Zhu X, Pan Z, Hao W, Li D, Zheng Q and Tang X: Luteolin potentiates low-dose oxaliplatin-induced inhibitory effects on cell proliferation in gastric cancer by inducing G2/M cell cycle arrest and apoptosis. Oncol Lett. 23:162022. View Article : Google Scholar

21 

Lee BY, Timpson P, Horvath LG and Daly RJ: FAK signaling in human cancer as a target for therapeutics. Pharmacol Ther. 146:132–149. 2015. View Article : Google Scholar

22 

Seguin L, Desgrosellier JS, Weis SM and Cheresh DA: Integrins and cancer: Regulators of cancer stemness, metastasis and drug resistance. Trends Cell Biol. 25:234–240. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Vadlamudi RK, Sahin AA, Adam L, Wang RA and Kumar R: Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215. FEBS Lett. 543:76–80. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Yu D and Hung MC: Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene. 19:6115–6121. 2000. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Yang Z, Liu H, Song Y, Gao N, Gao P, Hui Y, Li Y and Fan T: Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma. Int J Mol Med 54: 77, 2024.
APA
Yang, Z., Liu, H., Song, Y., Gao, N., Gao, P., Hui, Y. ... Fan, T. (2024). Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma. International Journal of Molecular Medicine, 54, 77. https://doi.org/10.3892/ijmm.2024.5401
MLA
Yang, Z., Liu, H., Song, Y., Gao, N., Gao, P., Hui, Y., Li, Y., Fan, T."Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma". International Journal of Molecular Medicine 54.3 (2024): 77.
Chicago
Yang, Z., Liu, H., Song, Y., Gao, N., Gao, P., Hui, Y., Li, Y., Fan, T."Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma". International Journal of Molecular Medicine 54, no. 3 (2024): 77. https://doi.org/10.3892/ijmm.2024.5401
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Z, Liu H, Song Y, Gao N, Gao P, Hui Y, Li Y and Fan T: Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma. Int J Mol Med 54: 77, 2024.
APA
Yang, Z., Liu, H., Song, Y., Gao, N., Gao, P., Hui, Y. ... Fan, T. (2024). Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma. International Journal of Molecular Medicine, 54, 77. https://doi.org/10.3892/ijmm.2024.5401
MLA
Yang, Z., Liu, H., Song, Y., Gao, N., Gao, P., Hui, Y., Li, Y., Fan, T."Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma". International Journal of Molecular Medicine 54.3 (2024): 77.
Chicago
Yang, Z., Liu, H., Song, Y., Gao, N., Gao, P., Hui, Y., Li, Y., Fan, T."Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel‑resistant esophageal squamous cell carcinoma". International Journal of Molecular Medicine 54, no. 3 (2024): 77. https://doi.org/10.3892/ijmm.2024.5401
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