Tumor suppressor genes and their underlying interactions in paclitaxel resistance in cancer therapy

Abstract

ObjectivesPaclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction.MethodsUsing PubMed online database and Google web site, the terms “paclitaxel resistance” or “taxol resistance” or “drug resistance” or “chemotherapy resistance”, and “cancer” or “carcinoma”, and “tumor suppressor genes” or “TSGs” or “negative regulated protein” or “antioncogenes” were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions.ResultsWe identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance.ConclusionA further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.

Role of Survivin and p53 Expression in Response of Primary Culture of Ovarian Cancer Cells to Treatment With Chemotherapeutic Agents

“…Tumor suppressor genes play an important role in sensitivity to chemotherapeutic agents and also prevent abnormal cells from surviving. 32 In the present study, we found that p53 mRNA expression was downregulated in paclitaxel-treated ovarian cancer cells whereas upregulated with carboplatin-treated ovarian cancer cells in 2 cases. This suggests that paclitaxel is more effective than carboplatin, and their IC 50 carboplatin dose was greater than or equal to 80 Kg/mL, which is suggestive of resistance to carboplatin.…”

Procaine Induces Epigenetic Changes in HCT116 Colon Cancer Cells

“…One of these mechanisms postulates that demethylating agent such as procaine could activate tumor suppressor gene(s), which, in turn, enforce the cells to commit apoptosis [36, 37]. Other mechanisms suggest the activation of caspase-activated DNase (CAD), which degrades DNA after a cascade of activation processes [38].…”

Polyethylenimine-functionalized silver nanoparticle-based co-delivery of paclitaxel to induce HepG2 cell apoptosis

“…[21][22][23][24][25][26][27] PTX disrupts the tubulin-microtubule equilibrium, which is different from conventional anticancer drugs affecting nucleic acid synthesis to induce cancer cell death. 28,29 It is considered as an appropriate candidate for chemotherapy because PTX at low concentrations can exert antiangiogenic activity. 30 However, the major problem for the clinical efficacy of PTX is compromised by its poor water solubility, low permeability, and serious adverse effects.…”