DOWNREGULATION OF STK33 AND ITS EFFECTS ON THE PROLIFERATION, INVASION, AND APOPTOSIS OF ESOPHAGEAL CANCER CELLS BY REGULATING THE S6K1/RPS6/BAD SIGNALING PATHWAY

Shoujun Hu¹, Yannan Han¹, Jing Zhou¹, Chao Zhou², Zhongtao Sun^3*

¹Department of Thoracic Surgery, Fuyang People's Hospital of Anhui Province, Fuyang 236000, PR China - ²Shanghai Chest Hospital, Shanghai 200030, PR China - ³Fuyang People's Hospital of Anhui Province, Fuyang 236000, PR China

Objective: To analyze the effect of downregulation of stk33 on the proliferation, invasion, and apoptosis of esophageal cancer cells by regulating the S6K1/RPS6/BAD signaling pathway.

Methods: Cancer tissues and normal tissues adjacent to the cancer were collected from 33 patients with esophageal squamous cell carcinoma who underwent surgical treatment in our hospital. The expression levels of si-stk33 in the esophageal squamous cell carcinoma and normal tissues adjacent to the cancer were detected using real-time quantitative PCR. The Eca109 cells were cultured. The si-stk33 plasmid was transfected into the cells and then cultured for 4 h to obtain the si-stk33 group. Control group cells were set, with 5 duplicate groups for each group. The expression levels of si-stk33 in the si-stk33 group and the control group were determined using real-time quantitative PCR and western blotting. The cell proliferation of each group was measured using the MTT method. The changes in the cell invasion ability and migration ability of the two groups were detected with a Transwell test and the changes in the cell cycle and apoptosis in each group with flow cytometry. The expression levels of p-S6K1, p-RPS6, and p-BAD in the two groups were determined using western blotting. 

Results: Compared with normal tissues adjacent to the cancer, the expression level of si-stk33 in esophageal squamous cell carcinoma was significantly higher (P<0.01). Compared with the control group, in the si-stk33 group cells, the expression level of si-stk33, the cell migration and invasion ability, the S-phase and G2-phase cells, and the expression levels of p-S6K1, p-RPS6, and p-BAD were significantly reduced, and the cells greatly increased at the G1 phase (P<0.01). There was no significant difference in OD value between the two groups at 24 h (P>0.05). From 48 h, the OD value of cells in the si-stk33 group was significantly reduced compared with that of the control group (P<0.01).

Conclusions: Downregulating the expression of stk33 can limit the proliferation, invasion, and metastasis of esophageal cancer cells, block the cell cycle at the G1 phase, and induce apoptosis by inhibiting the S6K1/RPS6/BAD signaling pathway.