SANGUINARINE PROMOTES OVARIAN CANCER CHEMOSENSITIVITY TO CISPLATIN BY BLOCKING THE EGFR/ERBB2 SIGNALING PATHWAY

Lin Chen¹, Ting Yang¹, Xinyuan Zhao^{2, *}

¹Department of Gynecology, The Second Affiliated Hospital of Xi 'an Medical College, Xi 'an 710038, Shaanxi Province, China - ²Department of Obstetrics, The Second Affiliated Hospital of Xi 'an Medical College, Xi 'an 710038, Shaanxi Province, China

Purpose: To investigate the effect of sanguinarine on the sensitivity of ovarian cancer to cisplatin by blocking the EGFR/erbB2 signal pathway. 

Methods: Human ovarian cancer cell line SKOV-3 was selected as the research object of this experiment. It was divided into a control group, a cisplatin group, a sanguinarine group, and a combination sanguinarine–cisplatin group (n = 5). The control group underwent no treatment (15% μL phosphate buffered saline), the cisplatin group was treated with only cisplatin (2.3 μg/L), the sanguinarine group was treated only with sanguinarine (2.2 μmol/L), and the combination sanguinarine–cisplatin group was treated with both sanguinarine and cisplatin (2.2 μmol/L + 2.3 μg/L). The purpose of the research was to study the inhibitory effect of different drugs on SKOV-3 ovarian cancer cells, the effect of SKOV-3 ovarian cancer cell apoptosis, and the effect on SKOV-3 ovarian cancer cells’ growth cycle. The expression of major EGFR/erbB2 genes signaling pathways and clone formation rate comparison in SKOV-3 ovarian cancer cells were detected and analyzed. 

Results: Compared with the control group, the number of necrotic cells and early and late apoptosis in the cisplatin group, the sanguinarine group, and the combination sanguinarine–cisplatin group were significantly higher, and the apoptosis of normal cells was fewer than that of the control group (P<0.05); however, the effect of sanguinarine combined with cisplatin was the most significant (P<0.05). Compared with the control group, the expression levels of areg, EGFR, pjun, pjnk, and Ki67 in the cisplatin group, the sanguinarine group, and the combination sanguinarine–cisplatin group were lower (P<0.05); however, the decrease of sanguinarine combined with cisplatin was the most significant (P<0.05). Compared with the control group, the inhibitory effects of the sanguinarine group, the cisplatin group, and the combination sanguinarine–cisplatin group on tumor cells became more obvious over time (P<0.05); however, the inhibitory effect of the combination sanguinarine–cisplatin group was more significant (P<0.05). Compared with the control group, the clone formation rates of the control group, cisplatin group, sanguinarine group, and combination sanguinarine–cisplatin group were significantly lower (P<0.05); however, the clone formation rate of combination sanguinarine–cisplatin group decreased significantly (P<0.05). Compared with the control group, the percentage of the cisplatin group in S phase decreased significantly, and the percentage in G2/M phase increased significantly (P<0.05). In the combination sanguinarine–cisplatin group, G0/G1 decreased significantly and G2/M increased significantly (P<0.05). Compared with the cisplatin group, the G2/M of the combination sanguinarine–cisplatin group decreased significantly, whereas the G0/G1 percentage increased significantly (P<0.05). 

Conclusion: Sanguinarine can improve the sensitivity of ovarian cancer cells to cisplatin chemotherapy, block the EGFR/erbB2 signal pathway, and reduce the drug resistance of cancer cells to chemotherapy drugs, thus providing a reference basis for the treatment of ovarian cancer.