ABSTRACT
Objective: To observe the relationship between stem cells marker CD90 and CDDP (cisplatin) resistance in lung adenocarcinoma A549 cells, and to explore whether CD90 is a marker of lung cancer stem cells. Methods: Self-renewal abilities of A549 and A549/CDDP cells were detected by sphere-forming assay, CCK-8 (cell counting kit-8) and plate colony-formation assay, respectively. The proportions of CD90+ in A549 cells, A549/CDDP adherent cells and the spheres cells were measured by FCM (flow cytometry). The CDDP resistance in CD90+A549 cells and CD90-A549 cells was detected by cytotoxicity experiment. The CDDP resistance in CD90+A549 cells in vivo was detected by using transplanted tumor in nude mice. Results: As compared with A549 cells, the abilities of sphere formation, proliferation and colony-formation efficiency of A549/CDDP cells were increased (P < 0.01). The proportions of CD90+ in A549/CDDP adherent cells and the sphere cells were higher than those in the corresponding A549 adherent cells and the sphere cells (P < 0.05). IC50 (half inhibitory concentration) values of CDDP in CD90+A549 and CD90-A549 cells were 8.50 and 1.50 μmol/L, respectively. The tumor xenograft volume of CD90 +A549 cells was larger than that of CD90-A549 cells after treatment with CDDP in nude mice (P < 0.05). Conclusion: A549/CDDP cells show high self-renewal ability and CD90+ proportion. CD90+A549 cells have high ability of CDDP resistance. CD90 may be a marker of lung cancer stem cells. Copyright © 2013 by TUMOR.
ABSTRACT
Chemotherapy is one of the main methods to treat malignant tumors in clinical practice. Resistance to antineoplastic agents is one of the important reasons for treatment failure. The antineoplastic mechanism of various chemotherapeutic agents is to cause DNA damage, then result in apoptosis of tumor cells. It is suggested that the function of DNA repair is directly associated with the efficacy of antineoplastic agents. Current studies suggest that there are four major DNA repair pathways including BER (base excision repair), NER (nucleotide excision repair), MMR (mismatch repair) and DSBR (double strand break repair). Of these four pathways, BER is one of the main mechanisms of DNA repair and its malfunction is closely related to the resistance to antineoplastic agents. Recently, many kinds of agents and strategies targeting BER have been developed to reverse chemoresistance. This review summarizes the progress in research in this area and discusses the mechanism of resistance to antineoplastic agents and the potential preventive and therapeutic strategies. Copyright © 2013 by TUMOR.