RESUMO
OBJECTIVE: To investigate the role of SRC kinase inhibitor PP2 in drug resistance to adriamycin (ADM) in breast cancer cells and invasion, metastasis of cells. METHODS: MTT assay was used to detect the inhibitory effect of ADM on MCF-7 and MCF-7/ADM cells. The 50% inhibitory concentration (IC50) and resistance index (RI) of cells were calculated. The expression of MDR1, connexin 43 (Cx43) and SRC proteins in breast cancer cells were detected by Western blot assay. Transwell experiment and cell scratch test were used to determine the invasion and migration of cells respectively [MCF-7, MCF-7/ADM, PP2 (1, 2, 4 µmol/L)]. Standard colony formation assay was used to detect the cytotoxicity effect of 4 µmol/L PP2 pretreatment on ADM. RESULTS: ADM inhibited the proliferation of MCF-7 more than MCF-7/ADM cells (P<0.01). The IC50 of MCF-7/ADM cells was 24.55 µmol/L, the IC50 of MCF-7/ADM cells was 770.57 µmol/L, the RI was 31. Compared with MCF-7 cells, expressions of the multidrug resistance proteins MDR1 and SRC were significantly increased (P<0.01). The invasion and migration ability of the MCF-7/ADM cells was stronger than that of the sensitive cells (P<0.01). When MCF-7/ADM was exposed to SRC inhibitor PP2, the invasion and metastasis ability of cells were inhibited (P<0.01) and the rate of colony formation was decreased, that is, more sensitivity to ADM (P<0.01). CONCLUSION: The resistance of MCF-7 to ADM is accompanied by increased expression of SRC. SRC inhibitor PP2 can reduce the cell resistance, ability of invasion and metastasis.