Yinjia pills inhibits the malignant biological behavior of HeLa cells through PKM2-medicated inhibition of JAK/STAT3 pathway.

Abstract

Cervical cancer is one of the most common tumors in women and is a major problem in gynecological health. Studies have shown that Yinjia pills (YJP), a traditional Chinese medicine, can effectively slow the progression of cervical cancer. Therefore, this study mainly explored the molecular mechanism by which YJP delays the progression of cervical cancer. The expression level of PKM2 in cervical cancer was evaluated by the gene expression profiling interactive analysis (GEPIA) database, and the prognostic value of the PKM2 gene was evaluated by the Kaplan‒Meier plotter database. HeLa cervical cancer cells were treated with different concentrations of YJP (2.5, 5, 10, and 20 mg/mL). The levels of the inflammatory factors were detected by ELISA. Cell proliferation activity, migration and invasion were detected by CCK-8 assay, Transwell assays and cell scratch experiment. Apoptosis was detected by flow cytometry. Western blotting was used to detect the expression of proteins. In this study, PKM2 was upregulated in both cervical squamous cell carcinoma (CESC) and endometrial adenocarcinoma tissues, and a Kaplan‒Meier analysis showed that higher PKM2 expression was associated with lower patient survival. YJP inhibited the proliferation, migration and invasion of HeLa cells in a dose-dependent manner, promoted the apoptosis of HeLa cells, and inhibited the expression of inflammatory factors. In addition, YJP inhibited the activation of the JAK/STAT3 pathway and the occurrence of EMT. Knockdown of PKM2 also inhibited the malignant biological behavior of HeLa cells, but overexpression of PKM2 weakened the inhibitory effect of YJP on the malignant biological behavior of HeLa cells. Angoline, a JAK/STAT3 pathway inhibitor, attenuated the effect of PKM2 overexpression on the efficacy of YJP. In conclusion, YJP can inhibit the activation of the JAK/STAT3 pathway by regulating PKM2, thereby inhibiting the malignant biological behavior of HeLa cells.