Cosuppression of HIF-1alpha and S1PR1 in order to inhibit cancer cell growth, in vitro

Abstract

Tumor microenvironment plays a very important role in cancer progression. There are many factors in the tumor area that can inhibit anti-tumor immune responses. In addition, many of these factors can increase the proliferation, angiogenesis and metastasis of cancer cells. Therefore, targeting these factors can be a good solution for cancer treatment. In this study, two very important factors in tumor microenvironment including HIF-1α and S1PR1 were targeted for treatment. Previous studies have shown that there is an interconnected network between HIF-1α and S1PR1. The aim of our study was to control this reinforcement loop. Materials and Methods: Alginate-conjugated trimethyl chitosan nanoparticles were prepared for effective transfer of siRNAs to cancer cells. We studied the effect of siRNA-loaded nanoparticles in vitro on the symptoms of 4T1 cancer cell line (breast cancer). The effect of combination therapy on survival and proliferation was assessed using MTT assay. Also, gene expression was assessed using real-time PCR test. Results: The results of this study showed that the produced nanoparticles had a size of about ~ 110 nm, PDI <0.2 and a zeta potential of 18 mV. In addition, combination therapy could well reduce the survival of cancer cells. Also, decreased cancer cell survival was associated with increased expression of Bax apoptotic gene and decreased expression of anti-apoptotic factor Bcl-2.