Pentoxifylline Sensitizes Cisplatin-Resistant Human Cervical Cancer Cells to Cisplatin Treatment: Involvement of Mitochondrial and NF-Kappa B Pathways

摘要: Background: Cervical cancer continues to be a major public health problem worldwide, and Cisplatin is used as first-line chemotherapy for this cancer; however, malignant cells exposed CISplatin (CIS) become insensitive the effects of drug. PenToXifylline (PTX) xanthine that sensitizes several types tumor apoptosis induced by antitumor drugs, such Adriamycin, Carboplatin, CIS. The PTX on have been related disruption NF-kappaB pathway, thus preventing activation cell survival mechanisms expression anti-apoptotic genes, secretion proinflammatory interleukins, growth factors. Objective: In work, we studied proprieties in human SiHa cervical carcinoma resistant Materials Methods: HeLa their CIS-resistant derived lines (SiHaCIS-R HeLaCIS-R, respectively) were in-vitro models. We alone or combination with CIS viability, apoptosis, caspase-3, caspase-8, caspase-9 activity, cleaved PARP-1, protein (Bcl-2 Bcl-xL) levels, p65 phosphorylation, cadmium chloride (CdCl2) sensitivity, Platinum (Pt) accumulation, glutathione (GSH) well gene GSH drug transporters (influx efflux). Results: sensitized SiHaCIS-R inducing caspase activation, PARP-1 cleavage. treatment also decreased increased Pt depleted GSH, downregulated ATP7A, ATP7B, GSR, MGST1 genes. Conclusion: reverses acquired phenotype resistance close sensitivity parental cells.