High expression of ABCG2 is associated with chemotherapy resistance of osteosarcoma

Abstract

Objectives Previous studies showed overexpression of ABCG2 in a variety of tumor tissues, which could potentially indicate the probability of chemotherapy resistance. This study aimed to reveal the role of ABCG2 in the development of chemotherapy resistance and the prognosis of osteosarcoma (OS). Methods Sixty-eight OS patients were included in this study. Tumor tissues were collected for each patient during surgery. DOX-resistant OS cell lines were induced by consecutive exposure of gradually increasing concentration of DOX to the parental cell lines. Lentivirus was used for the knockdown of ABCG2 in OS cells. Cells were treated with the gradient concentration of DOX, and the viability was assessed by CCK8 assay. Total RNA was isolated from the tumor tissues or tumor cells, and the expression of ABCG2 was analyzed by qPCR. The relationship between ABCG2 expression and clinicopathological characteristics of the patients was analyzed using Student’s t test or the Chi-square test. The overall survival time was calculated by the Kaplan-Meier method and analyzed by the log-rank test. p < 0.05 was considered statistically significant. Results DOX-resistant OS cells were successfully established through continuous exposure to DOX. Forty-eight hours after DOX exposure, the IC 50 value of DOX-resistant HOS cells and DOX-resistant U2OS was 3.5 μM and 3.25 μM, respectively. By contrast, those of the untreated HOS and U2OS cells were 1.15 μM and 0.93 μM, respectively (p < 0.01). The mRNA expression level of ABCG2 was significantly increased in DOX-resistant cell lines. The CCK-8 assay showed that the DOX-resistant HOS cells and DOX-resistant U2OS cells transfected with ShABCG2 were more sensitive to the DOX treatment than those transfected with ShCtrl. Analysis of gene expression in OS tissues showed remarkably higher expression of ABCG2 as compared with adjacent normal tissues (p < 0.01). Patients with high expression level of ABCG2 had obviously decreased overall survival time than the patients with normal expression (p < 0.01). Conclusions ABCG2 expression level was significantly associated with the resistance to chemotherapy and the overall survival of OS patients. ABCG2 may be a promising therapeutic target for OS patients.

Cancer Stemness/Epithelial–Mesenchymal Transition Axis Influences Metastasis and Castration Resistance in Prostate Cancer: Potential Therapeutic Target

“…Our group and others have found that the ABCG2 transporter is highly expressed in the spheres from PCa which correlates with a level of high drug resistance of this CSCs population [ 32 , 104 ]. In several other studies, the CSCs have showed to have a level of high resistance to multiple drugs including taxanes, tyrosine kinase and topoisomerase inhibitors, among others [ 4 , 105 , 106 , 107 ]. ALDH1, which is another stemness marker, has been implicated in changes in the metabolism of chemotherapeutic agents, reducing radio-sensitivity in the PCa cell lines [ 105 ].…”

The strategy and clinical relevance of in vitro models of MAP resistance in osteosarcoma: a systematic review

“…The search strategy employed in this review identified 18 clinical studies published between 1995-2021 that assessed expression of one gene [74], 12 proteins [26,28,36,48,[75][76][77][78][79][80][81][82][83] and ten ncRNAs [82,[84][85][86][87] in relation to relapse, metastasis and response to MAP therapy in OS patients (Table 4). Eight of these proteins overlapped with factors investigated in cell models of chemoresistance.…”

“…Seven studies investigated more than one patient outcome measure, two studies used both biopsy and surgical samples and one study used biopsy and relapsed samples. Response was used as a patient outcome measure in 17 studies and all were defined by the standard percentage necrosis threshold [26,28,36,48,[74][75][76][77][78][79][80][81][82][84][85][86][87]. Relapse as a patient outcome measure was variably defined with 1/7 studies using local relapse only [81], 2/7 studies including relapse at any site [77,79] and the remaining studies providing no clear definition [36,76,80,83].…”

“…Seventeen studies included in this review investigated differential expression of one gene, 11 proteins and ten ncRNAs in relation to patient response defined by necrosis [26,28,36,48,[74][75][76][77][78][79][80][81][82][84][85][86][87]. One study used a preliminary and validation cohort [82] whilst a No second study used an initial osteoblastic cohort followed by a validation cohort with mixed subtypes [85].…”

Heparin and Heparin-Based Drug Delivery Systems: Pleiotropic Molecular Effects at Multiple Drug Resistance of Osteosarcoma and Immune Cells

“…However, several studies have investigated the regulatory mechanism underlying ABCG2 expression in OS [ 79 , 80 ]. An association was found between high ABCG2 expression in patients with OS and poor survival and response to chemotherapy [ 81 ]. The role of ABCG2 in OS prediction was also established [ 80 ].…”