Berberine Combined with Formononetin Induces Autophagy Through Downregulation of the MAPK/ERK Signaling Pathway and Inhibits the Proliferation of Nasopharyngeal Carcinoma Cells

Abstract To investigate whether the combination of berberine and formononetin can inhibit the proliferation of nasopharyngeal carcinoma cells by regulating the MAPK/ERK signaling pathway and affecting cell autophagy. Methods: RTCA and CytationTM 5 cell imaging systems were used to detect cell proliferation. MDC staining and transmission electron microscopy were used to detect cell autophagy. Western blot was used to detect the expression levels of autophagy and proliferation-related proteins and the expression levels of key proteins in the MAPK/ERK signaling pathway. Results: The combination of berberine and formononetin can inhibit the proliferation of nasopharyngeal carcinoma cells (P < 0.05) and induce autophagy (P < 0.05) and. After berberine combined with formononetin for 24 h, the expression of LC3 II/I and Beclin1 increased, whereas the expression of P62 and PCNA decreased. The expression of key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway was downregulated (P < 0.05). Inhibiting autophagy or activating the MAPK/ERK signaling pathway significantly reduced the effect of berberine combined with formononetin on upregulating the expression of LC3 II/I and Beclin1 and downregulating the expression of P62 and PCNA. At the same time, it significantly reduced the effects of berberine combined with formononetin in inducing autophagy and inhibiting cell proliferation (P < 0.05). Conclusion: Berberine combined with formononetin inhibits the proliferation of nasopharyngeal carcinoma cells by downregulating the activity of the MAPK/ERK signaling pathway and then upregulating LC3 II/I and Beclin1, and downregulating the expression of P62 and PCNA.