Sam68 reduces cisplatin-induced apoptosis in tongue carcinoma.

Shimin Zhuang,Ming Song,Xidi Wang,Wenkuan Chen,Ji Zhang,Huan Li,Fan Gao,Shuwei Chen

doi:10.1186/s13046-016-0390-3

Abstract

BackgroundResistance to anticancer agents is a major obstacle for successful chemotherapy in tongue squamous cancer. Sam68 is an oncogenic-related protein in oral tongue squamous cell carcinoma functions as a signaling molecule mediating apoptosis, whose over-expression is associated with the clinicopathologic characteristics and prognosis of patients. The present study was to examine the effect of Sam68 on chemotherapeutics-induced apoptosis in oral tongue squamous cell carcinoma, and its clinical significance in oral tongue squamous cell carcinoma progression.MethodsThe effect of Sam68 on apoptosis induced by cisplatin was examined both in vitro and in vivo, using Annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays. Real-time PCR and Western blotting analysis were used to detect mRNA and protein expression levels.ResultsUpregulation of Sam68 significantly inhibited cisplatin-induced apoptosis in oral tongue squamous cell carcinoma cells, associated with induction of anti-apoptotic proteins caspase-9, caspase-3, and PARP. In contrast, Silencing Sam68 expression significantly enhanced the sensitivity of oral tongue squamous cell carcinoma cells to apoptosis induced by cisplatin both in vitro and in vivo.ConclusionsThe current study suggests that Sam68 could enhance the anti-apoptosis activity of oral tongue squamous cell carcinoma cells. Sam68 is a potential pharmacologic target for the treatment of oral tongue squamous cell carcinoma and inhibition of Sam68 expression might represent a novel strategy to sensitize oral tongue squamous cell carcinoma to chemotherapy.

Highlights

Resistance to anticancer agents is a major obstacle for successful chemotherapy in tongue squamous cancer
The current study suggests that Src-associated protein in mitosis (Sam68) could enhance the anti-apoptosis activity of oral tongue squamous cell carcinoma cells
In this study, we investigated the relationship between Sam68 status and responses to chemotherapy both in vitro and in vivo and evaluated the predictive value of Sam68 expression in oral tongue squamous cancer cell (OTSCC) cell lines treated with the DNA-damaging chemotherapeutic drug cisplatin

Summary

Introduction

Resistance to anticancer agents is a major obstacle for successful chemotherapy in tongue squamous cancer. Sam is an oncogenic-related protein in oral tongue squamous cell carcinoma functions as a signaling molecule mediating apoptosis, whose over-expression is associated with the clinicopathologic characteristics and prognosis of patients. The 5-year survival rate for Cisplatin-based chemotherapy (DDP), as a common standard therapeutic approach, plays an important role in tongue cancer treatment and results in many therapeutic benefits, including reducing tumor size, inhibiting the formation of distant metastatic lesions, and prolonging patient survival [6]. Resistance to anticancer agents is a major challenge for achieving successful chemotherapy in tongue cancer and can result in more aggressive tumor behavior and poor clinical outcomes [7, 8]. The molecular basis of resistance to chemotherapy is complex and involves various biological processes, such as drug transport, drug metabolism, apoptosis, and DNA

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Conclusion