Effects of different combined regimens of cisplatin, metformin, and quercetin on nasopharyngeal carcinoma cells and subcutaneous xenografts

Zhongwei Chen,Ying Zeng,Lianzhong Luo,Qihuang Lin,Xuan Hong,Shanshan Zhu,Zhen Zeng

doi:10.1038/s41598-020-80198-0

Abstract

Cisplatin, metformin, and quercetin are all reliable anticancer drugs. However, it is unclear how effective their different combination regimens are on the growth of nasopharyngeal carcinoma cell line Sune-1 and subcutaneous xenograft in nude mice. This study evaluated the effects of single-drug, two-drug, and three-drug simultaneous or sequential combined application of these drugs on the growth of Sune-1 cells and subcutaneous xenograft tumors in nude mice. The results showed that the different combination regimens of cisplatin, metformin and quercetin all had significant inhibitory effects on the proliferation of Sune-1 cells and the growth of subcutaneous xenografts in nude mice (P < 0.01), and the inhibition rate of the three drugs simultaneous combined application was significant Higher than the two-drug combination or single-drug application (P < 0.05), the contribution level of each drug in the three-drug combination application from high to low were cisplatin > metformin > quercetin. In summary, our results indicate that the simultaneous combination of cisplatin, metformin, and quercetin may synergistically inhibit the growth of Sune-1 cells and subcutaneous xenografts in nude mice through their different anticancer mechanisms, which may be clinically refractory and provide reference for chemotherapy of patients with recurrent nasopharyngeal carcinoma.

Highlights

Resist KRAS/LKB1 co-mutant tumors, and may prevent or delay the onset of cisplatin resistance by targeting CD133+ cancer stem cells[9]
The proliferation inhibitory effect of different concentrations of cisplatin, metformin, and quercetin on Sune-1 cell line was determined by Cell Counting Kit-8 (CCK-8) experiment
The results showed that the inhibitory effects of cisplatin, metformin, quercetin on Sune-1 cells increased with increasing concentration

Summary

Introduction

Resist KRAS/LKB1 co-mutant tumors, and may prevent or delay the onset of cisplatin resistance by targeting CD133+ cancer stem cells[9]. Some studies have proved that quercetin has significant anti-tumor activity, which can inhibit cancer cell proliferation, induce cancer cell apoptosis, interfere with cancer cell cycle and signal transduction pathways, and reverse cancer cell multidrug r esistance[11]. Some studies have shown that the combined use of quercetin and cisplatin can significantly increase the inhibitory effect on cancer. Xin Li and other studies have found that the combined use of quercetin and cisplatin can inhibit the phosphorylation of Akt and IKKβ, and cause Inhibition of NF-κB and anti-apoptotic protein xIAP, thereby inhibiting the growth of oral squamous cell carcinoma in mice[12]. Zhao et al found that quercetin has inhibitory activity on hepatocellular carcinoma cells through p16-mediated cell cycle arrest and apoptosis, and its combination with cisplatin has a synergistic inhibitory effect in inhibiting cell growth and inducing a poptosis[13]. We used the Cell Counting Kit-8 (CCK-8) to evaluate the effects of different combined regimens of cisplatin, metformin, and quercetin on the proliferation of Sune-1 cells, as well as the effects on human nasopharyngeal carcinoma subcutaneous xenografts, to provide a theoretical reference for the chemotherapy of patients with clinically refractory and recurrent nasopharyngeal carcinoma

Methods

Results

Conclusion