Toosendanin induces apoptosis in Oral Squamous Cell Carcinoma cells through inhibition of p-STAT3 and inhibits tumor growth in a OSCC-PDX model

Abstract

Abstract BACKGROUND Toosendanin (TSN) has been found to inhibit the proliferation of different types of tumor cell lines. However, there is no data on the role of TSN in oral squamous cell carcinoma (OSCC). The purpose of this study was to evaluate the effects of TSN on OSCC cells in vitro, and to verify its effects on oral squamous cell carcinoma in vivo in a patient-derived xenograft (PDX) model. METHODS The effect of TSN on OSCC cells was investigated by cytotoxicity assays and flow cytometry. The expression of proteins was detected by Western blotting. An OSCC PDX model was constructed to further study the role of TSN in regulating the function of oral squamous cell carcinoma. RESULTS The cell viability of CAL-27 and HN-6 cells decreased gradually when the concentration of TSN increased from 0.025µM and 0.05µM to 0.1µM, and the apoptosis rate increased. Compared with the control group, the cytotoxic effect of TSN on CAL-27 and HN-6 cells was enhanced in a dose-dependent manner, and it could inhibit proliferation and induce apoptosis at lower doses. TSN can also induce apoptosis by inducing cell cycle arrest and regulating the expression of proteins such as STAT3. After successfully constructing an OSCC-PDX model with high pathological homology to the primary tumor and treated with intraperitoneal injection of TSN, The results showed that TSN could significantly reduce the tumor size of PDX model mice without obvious toxicity. CONCLUSIONS The in vivo experiments showed that TSN has a significant inhibitory effect on tumor growth, suggesting that it may be a promising drug for the treatment of oral squamous cell carcinoma. TSN may be an effective potential anticancer drug for the treatment of oral squamous cell carcinoma.