JDHY3 Inhibits Hypopharyngeal Carcinoma Cell Proliferation and Promotes Apoptosis by Inhibiting the PI3K/AKT Pathway

Abstract

Background: Jieduhuayu No.3 (JDHY3) is a modified Chinese herbal formula beneficial for treating hypopharyngeal carcinoma (HC), but its pharmacological mechanism is unknown.

Objective: This study aimed to explore the mechanism of the herbal formula JDHY3 in inhibiting cell proliferation and promoting apoptosis in HC in vitro and in vivo.

Methods: In this study, HC cells were treated with cisplatin and different concentrations of JDHY3. The apoptosis rate was detected by flow cytometry. Western blotting was used to detect the proteins related to cell proliferation and apoptosis. Afterward, the xenograft mouse model was established and treated with cisplatin and JDHY3. Mouse tumour volume was measured, and the tumour tissues were assessed by HE staining and immunohistochemistry.

Results: JDHY3 significantly inhibited the proliferation of FaDu and Detroit-562 cells. In addition, JDHY3 significantly increased the apoptosis rate of HC cells and downregulated p-PI3K and p-Akt. In addition, JDHY3 upregulated the expression of the apoptosis-promoting proteins Bax, P53, and cleaved caspase-3. In addition, the expression of the antiapoptotic protein Bcl-2 was downregulated. Coincubation with SC79 attenuated the decrease in cell proliferation induced by JDHY3, further confirming that the proapoptotic effect of JDHY3 is associated with the inhibition of PI3K/Akt pathway activation.

Conclusions: The results of in vivo experiments showed that JDHY3 could effectively inhibit the proliferation of HC cells, and HE staining showed that JDHY3 reduced the invasion of HC cells. Immunohistochemistry showed that the expression of P53 and cleaved caspase-3 was significantly increased in the tissues of the JDHY3-treated group.

Keywords: Hypopharyngeal carcinoma; JDHY3; PI3K/Akt pathway; apoptosis; immunohistochemistry; proliferation.