STI 571增强非小细胞肺癌对顺铂的敏感性

STI 571 potentiates the sensitivity of non-small cell lung cancer cell line A549 to cytotoxic effects of cisplatin in vitro

目的:比较STI 571单药及联合顺铂(DDP)对非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞株A549及其DDP耐药株(A549/DDP)的增殖、细胞周期和凋亡的影响以及STI 571相关受体在NSCLC组织中的表达。方法:体外培养A549和A549/DDP细胞,应用MTT法测定STI 571和(或)DDP对细胞的增殖作用;通过FCM法分析细胞周期和凋亡;应用免疫细胞化学和免疫组织化学染色分别测定A549细胞株和NSCLC组织中STI 571相关受体的表达。根据Kaplan-Meier生存曲线,比较血小板衍化生长因子受体(platelet-derived growth factor receptor,PDGFR)-α和-β的表达与NSCLC患者总体生存的关系。结果:STI 571单药对A549/DDP细胞有增殖抑制作用,能增强细胞对DDP的敏感性,增加A549/DDP细胞的G2/M期和S期的细胞数,诱导其凋亡。STI 571在<10μmol/L时,对A549细胞增殖无明显影响。A549细胞和A549/DDP细胞均表达PDGFR-α和-β,后者还表达c-KIT蛋白。在肺腺癌中,PDGFR-α和PDGFR-β的表达率分别为65.5%和69.0%,与肺鳞癌的70.4%和74.1%相似,仅1例肺鳞癌表达c-KIT(3.7%)。表达PDGFR-α和-β的患者3年生存率和总体生存与不表达患者相似。结论:STI 571可以抑制DDP耐药的NSCLC细胞株的增殖,诱导其凋亡,并能增加DDP耐药细胞对DDP的敏感性。在NSCLC患者中,PDGFR-α和-β的表达水平与预后无关。

Objective ： This study was designed to compare the effects of STI 571 on proliferation, cell phases, and apoptosis between A549 and cisplatin-resistant A549 cells （A549/DDP） and detect the expressions of STI 571-related receptors in non-small cell lung cancer （NSCLC） tissues. Methods： A549 and cisplatin-resistant A549 cells （A549/DDP） were cultured in vitro, The cell proliferation was measured by MTT assay. Cell cycle distribution and apoptosis induced by STI 571, cisplatin and their combination were detected by flow cytometry in NSCLC cell lines. The expressions of platelet-derived growth factor receptor （PDGFRs） -α and- β and c-KIT in the non-small cell lung cancer cell lines and tissues were investigated by immunocytochemistry and immunohistochemistry, respectively. Kaplan-Meier survival curves were used to compare the correlation of PDGFR-α and-β expression with total survival of NSCLC patients. Results： STI 571 inhibited proliferation of A549/DDP cells, sensitized them to cisplatin chemotherapy, increased the cell number in G2/M and S phase, and induced apoptosis. However, STI 571 at the concentration below 10 μmol/L had no effect on the proliferation of A549 cells. Both A549 and A549/DDP cells expressed PDGFR-α and-β, but c-KIT expression was only observed in A549/DDP cells. The expression rates of PDGFR-α and-β were 65.5% and 69% in pulmonary adenocarcinoma, similar to those in squamous carcinoma （70.4% and 74.1% ）. Only one case of squamous carcinoma expressed c-Kit （3.7%）. The PDGFR-α or β-positive patients had similar 3-year survival rates and overall survival time with the PDGFRα or β-negative patients. Conclusion： STI 571 could suppress proliferation of A549/DDP cells, induce apoptosis and increase the sensitivity of A549/DDP to cisplatin. The levels of PDGFRα and β expression did not correlate with the prognosis of NSCLC patients.