Opsin3 sensitizes hepatocellular carcinoma cells to 5-fluorouracil treatment by regulating the apoptotic pathway.
Hepatocellular carcinoma (HCC) is the third most common cancer worldwide, causing over 0.5 million deaths per year, with approximately half of these in China. Chemotherapy is the optimal treatment for patients with advanced HCC, although chemoresistance has become a significant obstacle to successful anti-cancer therapy. The expression of opsin3 (OPN3), also called encephalopsin or panopsin, is lower in 5-fluorouracil (5-FU)-resistant Bel7402(5-FU) cells compared to 5-FU-sensitive Bel7402 cells. To explore the role of OPN3 in 5-FU resistance, OPN3 overexpressing (Bel7402(5-FU)-OPN3) and knockdown (Bel7402-RNAi-OPN3) cell lines were generated. Bel7402(5-FU)-OPN3 cells were more sensitive to 5-FU treatment than controls, while OPN3 knockdown resulted in a significant increase in 5-FU resistance. This result was replicated in a second HCC cell line, HepG2. Further investigation of the mechanism revealed that decreased OPN3 levels in Bel7402(5-FU) cells activated the anti-apoptotic pathway through increasing phospho-Akt and the Bcl2/Bax ratio, while overexpression of OPN3 inactivated this pathway. Taken together, these results suggest that OPN3 depletion is involved in 5-FU resistance, and that therapeutic strategies targeting OPN3 may improve HCC sensitivity to chemotherapy.
Department of Pathogen Biology, Nanjing Medical University, Jiang Su, Nanjing 210029, People's Republic of China.
Jianhua
J
Jiao
Shanchao
S
Hong
Jin
J
Zhang
Lei
L
Ma
Yan
Y
Sun
Donghui
D
Zhang
Bo
B
Shen
Changliang
C
Zhu
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017299:Rod Opsins / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; C430099:OPN3 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017299:Rod Opsins; D051028:bcl-2-Associated X Protein; D005472:Fluorouracil