Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo.
Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo.
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DOI：
10.1016/j.apsb.2016.06.005
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Fu F
中科院分区：
文献类型：
--
作者：
Lv G;Sun D;Zhang J;Xie X;Wu X;Fang W;Tian J;Yan C;Wang H;Fu F
微管蛋白已被证明是开发抗前列腺癌细胞毒性药物的有效靶标。此前，我们报道了Lx2-32c是一种与微管蛋白具有高结合亲和力的抗微管蛋白剂。在这项研究中，我们研究了 Lx2-32c 作为有效细胞毒剂治疗前列腺癌的潜力。 MTT 测定表明，Lx2-32c 对所有测试的前列腺癌细胞系均具有细胞毒性。 Lx2-32c 处理的细胞通常表现出与细胞凋亡开始相关的圆形形态，如免疫细胞化学染色所证明的。用 Lx2-32c 停滞在细胞周期的 G2/M 期处理的人前列腺癌细胞系，通过流式细胞术测定，该处理与处于亚 G0/G1 期的细胞比例增加相关。此外，通过蛋白质印迹测定显示了用Lx2-32c处理的前列腺癌细胞系中聚(ADP-核糖)聚合酶的切割形式的表达。 LNCaP和PC3衍生肿瘤在裸鼠中的异种移植表明，Lx2-32c治疗显着抑制肿瘤生长，其效果与多西他赛相当。这些发现证明了 Lx2-32c 作为治疗前列腺癌的候选抗肿瘤药物的潜力。一种新型微管聚合剂 Lx2-32c 可以将前列腺癌细胞阻滞在 G2/M 期，并通过破坏微管动力学来诱导细胞凋亡。该化合物在体内也显示出抗肿瘤功效。
Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer. A novel microtubule-polymerizing agent, Lx2-32c, can arrest prostate cancer cells in the G2/M phase and induce cell apoptosis by disrupting microtubule dynamics. This compound also displays antitumor efficacy in vivo.
影响因子：
3.7
作者：
Wang H;Zhang J;Lv G;Ma J;Ma P;Du G;Wang Z;Tian J;Fang W;Fu F
通讯作者：
Fu F