Effects of bosutinib on the malignant behavior of thyroid papillary carcinoma B-CPAP cells and its mechanisms

Abstract

Objective: To investigate the effects of bosutinib on the malignant behavior of thyroid papillary carcinoma B-CPAP cells and its possible mechanisms. Methods: Thyroid papillary carcinoma B-CPAP cells were cultured in vitro with a concentration gradient of(1、2、3、4 and 5 μmol/L)bosutinib intervened for 24 hours, DMSO was used as the control group. Five parallel compound holes were set in each group. Cell counting kit (CCK-8 method) method was used to detect cell proliferation. Transwell assay and cell wound healing assay were used to detect cell invasion and migration. TUNEL staining assay and flow cytometry were used to detect cell apoptosis. Western blot was used to detect the expressions of autophagic proteins (Beclin-1, LC3, p62) and signal pathway proteins (SIK2, p-mTOR, mTOR, p-ULK1, ULK1). Results: Compared with the control group, the cell proliferation activity, migration ability and invasion ability were decreased (P＜0.01), while the cell apoptosis rate was increased (P＜0.01) in the bosutinib concentration groups of 2, 3, 4 and 5 μmol/L . In the concentration groups of 4 and 5 μmol/L, the expression of Beclin-1 (P＜0.05), LC3- Ⅱ/LC3- Ⅰ (P＜0.05), SIK2 (P＜0.01) and p-ULK1 (P＜0.01) protein was decreased, while the expression of p62 (P＜ 0.05) and p-mTOR (P＜0.01) protein was increased. Conclusion: Bosutinib may inhibit the autophagy of thyroid papillary carcinoma cells through SIK2-mTOR-ULK1 signaling pathway to inhibit their proliferation, invasion and migration and promote apoptosis, thereby weakening their malignant behavior.