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5-flurouracil (5-FU)-based chemotherapy is the main pharmacological therapy for advanced colorectal cancer (CRC). Despite significant progress in the treatment of CRC during the last decades, 5-FU drug resistance remains the most important cause of failure in CRC therapy. Resistance to 5-FU is a complex and multistep process. Different mechanisms including microsatellite instability, increased expression level of key enzyme thymidylate synthase and its polymorphism, increased level of 5-FU-activating enzymes and mutation of TP53 are proposed as the main determinants of resistance to 5-FU in CRC cells. Recently, micro-ribonucleic acids (miRNA) and their alterations were found to have a crucial role in 5-FU resistance. In this regard, the miRNA-mediated mechanisms of 5-FU drug resistance reside among the new fields of pharmacogenetics of CRC drug response that has not been completely discovered. Identification of the biological markers that are related to response to 5-FU-based chemotherapy is an emerging field of precision medicine. This approach will have an important role in defining those patients who are most likely to benefit from 5-FU-based chemotherapy in the future. Thereby, the identification of 5-FU drug resistance mechanisms is an essential step to predict and eventually overcome resistance. In the present comprehensive review, we will summarize the latest knowledge regarding the molecular determinants of response to 5-FU-based chemotherapy in CRC by emphasizing the role of miRNAs.

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Introduction: Resistance to chemotherapy and severe side effects have been reported as the main reasons for treatment failure in patients with cervical cancer. Therefore, it is necessary to find new treatment strategies with fewer side effects and more efficacy. This study aimed to investigate the cytotoxic property of tin (IV) oxide (SnO2) nanoparticles (NPs) against human cervical cancer cells (HeLa cells). In addition, the molecular mechanism of anticancer activity of SnO2 NPs was evaluated. Materials and Methods: The cytotoxicity of SnO2 NPs against HeLa cells and normal mouse fibroblast cells (L929) was studied using an MTT assay. To determine the mechanism of action of SnO2 NPs, the cells were treated with the half maximal inhibitory concentration values of SnO2 NPs for 24 h and apoptotic cell percentage was assessed by Annexin-PI and flow cytometry. In addition, real-time quantitative polymerase chain reaction (PCR) was used to evaluate the mRNA expression levels of apoptotic genes (Bax and Bcl-2). Results: SnO2 NPs suppress the viability of HeLa cells in a dose-dependent manner. This compound was more cytotoxic against HeLa cells than L929 cells. Flow-cytometry analysis revealed that SnO2 NPs significantly caused cell growth arrest. Moreover, real-time PCR results showed that SnO2 NPs treatment decreased Bcl-2 and increased Bax expression level. Conclusion: SnO2 NPs treatment significantly inhibit HeLa cells viability through the induction of apoptosis. Interestingly SnO2 NPs were more cytotoxic against HeLa cells than normal fibroblast cells, which may provide promising evidence for their applications as an anticancer drug.