Role of P53 Mediated Molecular Regulation in Starvation-Induced Autophagy in HCT-116 and HT-29 Colorectal Carcinoma Cells

The tumor suppressor P53 is a known regulator of autophagy, which has been reported to be associated with colorectal cancer (CRC) cells' drug resistance. However, the molecular mechanisms of P53 regulating autophagic responses remain incompletely clear in CRC. HCT-116 and HT-29 cell line are colorectal cancer cell line with wild type and mutant P53 gene. Here, we aimed to investigate the mechanisms of P53 regulating the starvation-induced autophagy in HCT-116 and HT-29 cells. After P53 was inhibited by siRNA following treatment with EBSS or EBSS combination with bafilomycin A1, the hallmarks of autophagy were examined by real-time PCR and western blot. We found that P53 knockdown led to the accumulation of p62 in HCT-116 cells, indicating the autophagy flux was blocked. In addition, P53 knockdown caused the decreased p62 in HT-29 cells and the autophagy flux was activated. Furthermore, the expression of signaling pathway genes and autophagy related genes (ATG) showed an opposite pattern between two cell lines after P53 inhibition. Specially, the expression of autophagy regulating genes ATG14, VPS34 and TSC1 were significantly decreased by P53 knockdown in HCT-116 cells, and the expression of PTEN, DRAM1 and ULK2 were dramatically increased in HT-29 cells. In conclusion, our results demonstrated that P53 can promote autophagy by increasing the expression of signaling pathway genes and ATG in HCT-116 cells but inhibit autophagy by an opposite pattern in HT-29 cell line. These findings might be hopeful for the targeting therapy of different types of CRC.