MCR肽MCR-4和MCR-14对化疗耐药人小细胞肺癌的体内有效抗肿瘤活性

R T Radulescu, G Jaques
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摘要

既往研究表明,以视网膜母细胞瘤蛋白(retinoblastoma protein, RB)片段LFYKKV为活性位点的MCR肽在体外和体内均能抑制人非小细胞肺癌(NSCLC)细胞的增殖。本研究的目的是在体内测试这些化合物对人小细胞肺癌(SCLC)的治疗作用,因为这种肿瘤对常规治疗是出了名的耐药,或者在最初成功治疗后迅速复发。我们在此报道了MCR肽MCR-4和MCR-14在裸鼠中对rh阴性H82 SCLC异种移植肿瘤显示出有效的抗增殖活性,而在临床相关剂量下并行测试的化疗药物VP-16没有抗肿瘤作用。这些令人鼓舞的结果保证在不久的将来加速将MCR肽引入rb阴性肿瘤(如SCLC)患者的临床试验。
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Potent in vivo antineoplastic activity of MCR peptides MCR-4 and MCR-14 against chemotherapy-resistant human small cell lung cancer.

Previous studies have shown that MCR peptides possessing the retinoblastoma protein (RB) fragment LFYKKV as the active site are able to inhibit the proliferation of human non-small cell lung cancer (NSCLC) cells in vitro and in vivo. The goal of the present study was to test these compounds against human small cell lung cancer (SCLC) in vivo since this tumor is notoriously resistant to conventional therapy or, respectively, is characterized by rapid relapse after initially successful treatment. We herein report that the MCR peptides MCR-4 and MCR-14 display potent antiproliferative activity against RB-negative H82 SCLC xenograft tumors in nude mice, whereas the chemotherapeutic agent VP-16 tested in parallel in a clinically relevant dose had no anti-tumor effect. These encouraging results warrant accelerating the introduction of MCR peptides into clinical trials in patients with RB-negative tumors such as SCLC in the near future.

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