Carbonyl cyanide 3-chlorophenylhydrazone promotes of mitophagy in gastric cancer cells MKN1 and MKN45 via PINK1/parkin pathway

BACKGROUND Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), as a common mitochondrial uncoupling agent, inducer of mitochondrial autophagy, has been used in nervous system and digestive system diseases. Mitochondrial autophagy is rarely reported in gastric cancer (GC). In this study, we used CCCP to treat MKN1 and MKN45 gastric cancer cells. METHODS We studied its effects on cell viability, migration and invasion, mitochondrial membrane potential level, apoptosis, cell cycle and mitophagy of GC were determined respectively by CCK8, Wound-Healing, Transwell, JC-1 dye, Western blot analysis and Flow cytometry assays. CCCP drugs and saline were injected intravenously, respectively, to clarify the effects of the drugs on HGC27 xenograft tumours in nude mice. RESULTS CCCP significantly inhibited the activity of MKN1 and MKN45 cells in a dose-dependent manner, and inhibited cell proliferation, migration and invasion. CCCP induced MKN1 and MKN45 cell apoptosis and arrested cell cycle in G1 phase. Furthermore, CCCP inhibited the expression of CyclinD1, CDK4 and CDK6, thus inhibited the cell cycle, and promoted the decline of mitochondrial membrane potential, which induced cells to enter PINK1 / parkin pathway mitophagy. Intravenous CCCP drugs significantly inhibited nude mouse HGC27 xenograft tumour Growth. CONCLUSIONS In general, CCCP, can regulate gastric cancer cells by inducing mitophagy, and may be a potential therapy for gastric cancer.