ATP7B expression is associated with in vitro sensitivity to cisplatin in non-small cell lung cancer

Abstract

Abstract. copper-transporting P-type adenosine triphosphatase (AtP7B) is reportedly associated with platinum drug resistance in various solid tumors. However, the impact of AtP7B on platinum drug resistance in non-small cell lung cancer (nsclc) remains unclear. We investigated in vitro cisplatin (cDDP) sensitivity using the collagen gel-droplet embedded culture drug sensitivity test. the AtP7B mrnA expression level in each specimen was also examined using real-time polymerase chain reaction. the relationship between AtP7B expression and in vitro cDDP sensitivity was then evaluated. the AtP7B mrnA expression levels in cDDPresistant tumors were significantly higher than those in the cDDP-sensitive group (p=0.015; Mann-Whitney U test). our results suggested that AtP7B expression is a promising chemoresistance marker for cisplatin. Introductionthe anticancer drug cisplatin (cDDP), which contains platinum, is widely used for the treatment of solid tumors such as testicular, ovarian, cervical, bladder, head and neck, as well as non-small cell lung cancer (nsclc) (1). cDDP has been a key drug in chemotherapy against nsclc for more than 20 years.However, the overall response rate to cisplatin as a single agent against nsclc is no more than 20% (2). Furthermore, the development of resistance to cDDP is common during treatment of nsclc patients, and is an important concern for clinical oncologists. thus, exploring chemoresistance markers is significant. Mechanisms of CDDP resistance include a decrease in drug accumulation and enhanced detoxification, but an increase in DNA repair efficiency. However, studies are mainly limited to in vitro or in vivo experiments and none of the examined markers have been validated as common contributors to clinical cDDP resistance or the prognosis of patients with nsclc (3).copper-transporting P-type adenosine triphosphatase (AtP7B) plays a key role in copper distribution inside cells. AtP7B is expressed in liver and kidney and, to a lesser extent, in the brain in normal individuals (4,5). AtP7B is responsible for the export of copper from the liver; thus, mutations that disable the function of AtP7B may lead to excessive hepatic copper accumulation, as suggested by the impairment of biliary copper excretion in patients with Wilson disease (6). Previous studies suggested that the copper export system functions as efflux transporters for platinum drugs. Moreover, the immunohistochemical expression of AtP7B has been shown to be associated with resistance to platinum drugs in certain solid tumors (3,(7)(8)(9). However, the expression of AtP7B and its impact on cDDP resistance in nsclc have yet to be thoroughly investigated.this study aimed to investigate the predictive value of AtP7B gene expression on in vitro chemosensitivity to cDDP, using surgically resected specimens from patients with nsclc. Materials and methodsStudy population. eligible patients included those with a histological diagnosis of nsclc. these patients had not received chemotherapy nor radiotherapy and had undergone surgic...

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Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells

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Copper efflux transporters ATP7A and ATP7B: Novel biomarkers for platinum drug resistance and targets for therapy

“…High ATP7B expression tends to increase the resistance to platinum drugs in cells, while silence of ATP7B enhances the sensitivity to platinum drugs (28)(29)(30)(31)(32). However, ATP7B levels appear to be higher in resistant group and are associated with chemotherapeutic response and prognosis in the patients receiving platinum-based chemotherapy (33)(34)(35)(36)(37)(38)(39)(40).…”