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Autophagy facilitates anticancer effect of 5-fluorouracil in HCT-116 cells
Jing-wen Yang1, Qing-huai Zhang1, Tong Liu2
1 Department of Anorectal Surgery, Tianjin Union Medicine Centre, Tianjin, P.R. China
2 Department of General Surgery, Institute of General Surgery, General Hospital, Tianjin Medical University, Tianjin, P.R. China
Correspondence Address:
Tong Liu,
No. 154, Anshan Road, Heping District, Tianjin 300070
P.R. China
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/0973-1482.204898
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Aim of Study: The roles of autophagy performed in chemotherapy-induced cell death or proliferation inhibition were still in debate. In this study, we aimed to disclose the function of autophagy in chemotherapy of HCT-116 colon cells.
Materials and Methods: Pharmacological and genetic methods were applied to induce and inhibit autophagy and elucidate the roles of autophagy performed in chemotherapy-induced proliferation inhibition and apoptosis. Autophagy was assessed by microtubule-associated protein light chain 3 (LC3) expression and monodansylcadaverine (MDC) staining.
Results: After treatment with 5-fluorouracil (5-FU), HCT-116 cells showed typical autophagy as stained by MDC. Autophagy inhibitor (3-methyladenine [3-MA]) or inducer (rapamycin) was applied in combination with 5-FU, respectively. As evidenced by our data, 3-MA inhibited while rapamycin facilitated 5-FU-induced apoptosis and proliferation inhibition of HCT-116 cells. Consistently, 3-MA inhibited, while rapamycin facilitated 5-FU-induced expressions of Beclin1 and LC3B. Moreover, 3-MA inhibited while rapamycin facilitated 5-FU-induced p53 protein expression. Using genetic method, Beclin1 overexpression increased while Beclin1 knockdown decreased 5-FU-induced cell proliferation inhibition and apoptosis. Especially, Beclin1 overexpression increased while Beclin1 knockdown decreased 5-FU-induced p53 expression.
Conclusion: Our study provides both of pharmacological and genetic evidence to support that autophagy facilitates anticancer effect of the chemotherapeutic agent. The associated application of autophagy inducer with 5-FU would be beneficial for the chemotherapy in HCT-116 cancer cells.
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