Adjusting autophagy to augment sensitivity of 5-FU in Bel-7402/FU cells

Abstract

Abstract: AIM: To explore the effects of autophagy in the sensitivity of Hepatocellular carcinoma cells line Bel-7402/FU to 5-FU.METHODS: Hepatocellular carcinoma cells lines Bel-7402 and Bel-7402/FU were treated with 5-FU or 3-MA, or pretreated with 3-MA followed by 5-FU. MTT method test was used to determine the proliferative inhibition rate. Flow cytometry was used to examine cell apoptosis. The GFP-LC3B morphological changes were observed by fluorescent microscope.RESULTS: The IC₅₀ values of 5-FU in Bel-7402 and Bel-7402/FU cells were 4.66 μg /mL and 68.14 μg /mL, respectively.The apoptosis rates of the Bel-7402 and Bel-7402/FU were 13.80% and 1.09%,respectively. When 5-FU was used combined with 3-MA, the IC₅₀ values of 5-FU in Bel-7402 and Bel-7402/FU cells were 4.31 μg /mL and 29.44 μg /mL. The apoptosis rates of Bel-7402 and Bel-7402/FU were 13.82% and 6.86%, respectively. 3-MA decreased 5-FU-induced punctuate spot formation in Bel-7402/FU.CONCLUSION: Autophagy is connected with 5-FU-resistance and inhibition of autophagy can reverse 5-FU-resistance in Bel-7402 /FU.

Key words: autophagy, apoptosis, hepatocellular carcinoma, 3-MA, 5-FU

CLC Number:

R965.2

WANG Meng, HUANG Can, YANG Cui, XIA Quan , XU Du-juan. Adjusting autophagy to augment sensitivity of 5-FU in Bel-7402/FU cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(5): 488-492.

References

[1] Zhang H, Ozaki I, Hamajima H, et al. Vitamin K2 augments 5-fluorouracil-inducedgrowth inhibition of human hepatocellular carcinoma cells by inhibiting NFkappaB activation[J]. Oncol Rep,2011, 25(7):159-166.
[2] Nagakawa H, Shimozato O, Yu L, et al. Expression of a murine homolog of apoptosis-inducing human IL-24/MDA-7 in murine tumors fails to induce apoptosis or produce anti-tumor effects[J]. Cellular Immunol, 2012, 275(1/2):90-97.
[3] Spaulding C, Guo W, Effros RB, et al. Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation[J]. Exp Gerontol, 2009, 34(5): 633-644.
[4] Bincoletto C, Bechara A, Pereira GJ, et al. Interplay between apoptosis and autophagy, a challenging puzzle: New perspectives on antitumor chemotherapies[J]. Chem Bio Interact, 2013, 206(2): 279-288.
[5] 刘飞,胡琴,吉兆宁. 多西紫杉醇诱导宫颈癌HeLa细胞自噬性凋亡的研究 [J].中国临床药理学与治疗学,2009,14(8):877-882.
[6] 郝刚,周芳,吴晓兰,等. AEG-1基因在肿瘤研究中的进展[J].中国临床药理学与治疗学,2011,16(6):679-687.
[7] Bhutia SK, Mukhopadhyay S, Sinha N, et al. Chapter two-autophagy: cancer's friend or foe[J] ？ Adv Cancer Res, 2013, 118: 61-95.
[8] Mai TT, Moon J, Song Y, et al. Ginsenoside F2 induces apoptosis accompanied by protective autophagy in breast cancer stem cells[J]. Cancer Lett, 2012,321(2): 144-153.
[9] Bauvy J, Hou N, Faried A, et al. Inhibition of autophagy by 3-MA enhances the effect of 5-FU-induced apoptosis in colon cancer cells[J]. Ann Surg 0ncoi, 2009, 16(3):761-771.
[10] Guo XL, Li D, Hu F, et al. Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells[J]. Cancer Lett, 2012, 320(2): 171-179.
[11] Kang R, Wang ZH, Wang BQ, et al. Inhibition of autophagy-potentiated chemosensitivity to cisplatin in laryngeal cancer Hep-2 cells[J]. Am J Otolaryng, 2012, 33(6): 678-684.

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