Journal of cancer research and therapeutics, 2018-12, Vol.14 (12), p.1141-1147
2018
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- Autor(en) / Beteiligte
- Titel
- Autophagy facilitates anticancer effect of 5-fluorouracil in HCT-116 cells
- Ist Teil von
- Journal of cancer research and therapeutics, 2018-12, Vol.14 (12), p.1141-1147
- Ort / Verlag
- India: Wolters Kluwer India Pvt. Ltd
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0973-1482eISSN: 1998-4138DOI: 10.4103/0973-1482.204898Titel-ID: cdi_proquest_journals_2157295371
- Format
- –
- Schlagworte
- Adenine - analogs & derivatives, Adenine - pharmacology, Antineoplastic agents, Antineoplastic Combined Chemotherapy Protocols - pharmacology, Antineoplastic Combined Chemotherapy Protocols - therapeutic use, Apoptosis, Apoptosis - drug effects, Autophagy, Autophagy - drug effects, Autophagy - genetics, Beclin-1 - genetics, Beclin-1 - metabolism, Biochemistry, Cancer, Cancer cells, Cancer therapies, Cancer treatment, Cell cycle, Cell death, Cell growth, Cell Proliferation - drug effects, Chemotherapy, Colorectal cancer, Colorectal Neoplasms - drug therapy, Colorectal Neoplasms - pathology, DNA damage, Dosage and administration, Drug Screening Assays, Antitumor, Drug Synergism, Drug therapy, Drugs, Fluorouracil, Fluorouracil - pharmacology, Fluorouracil - therapeutic use, Genetic aspects, Genetic research, HCT116 Cells, Humans, Kinases, Laboratories, Microtubule-Associated Proteins - metabolism, Proteins, Radiation therapy, RNA, Small Interfering - metabolism, Sirolimus - pharmacology, Sirolimus - therapeutic use, Studies, Tumors