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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 12  |  Page : 1141-1147

Autophagy facilitates anticancer effect of 5-fluorouracil in HCT-116 cells


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
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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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