Department of Pharmacy, Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu Province, China.
Toxicol In Vitro. 2011 Mar;25(2):513-20. doi: 10.1016/j.tiv.2010.11.009. Epub 2010 Nov 18.
Lung cancer, including lung metastatic cancer, remains one of the most difficult types of cancer to treat. Therefore, the search for new agents for its treatment is very important. 10-Hydroxycamptothecin (HCPT) was proved to have ideal anticancer activity in curing series cancer cells. In this study, the anticancer effect of HCPT on melanoma lung metastasis cancer was investigated by several administration routes, and whether the effect may be attributed to the induction of tumor cells apoptosis was determined. MTT assay results showed that HCPT exhibited selective cytotoxic activity against B16-F10 cells in a concentration- and time-dependent manner. Hoechst 33258 staining and transmission electron microscopy showed typical apoptotic morphology such as condensed chromatin, irregular nuclei, and apoptotic body formation. Flow cytometry analysis indicated a growth on apoptotic cells and a cell-cycle arrest in S phase after treatment with HCPT. In vivo melanoma pulmonary metastases were inhibited by treatment with HCPT. A more significant inhibition was observed if HCPT was administered by aerosol inhalation than that given by i.v. or i.p. administration. Thus, HCPT exhibited potential anticancer activity against B16-F10 cells in vitro and in vivo. However, the possible mechanisms involved still need to be investigated to explain this behavior.
肺癌,包括肺转移性癌症,仍然是最难治疗的癌症之一。因此,寻找新的治疗药物非常重要。10-羟基喜树碱(HCPT)已被证明在治疗多种癌细胞方面具有理想的抗癌活性。在这项研究中,通过多种给药途径研究了 HCPT 对黑色素瘤肺转移癌的抗癌作用,并确定了这种作用是否归因于诱导肿瘤细胞凋亡。MTT 检测结果表明,HCPT 对 B16-F10 细胞具有浓度和时间依赖性的选择性细胞毒性。Hoechst 33258 染色和透射电镜显示典型的凋亡形态,如染色质浓缩、核不规则和凋亡小体形成。流式细胞术分析表明,HCPT 处理后细胞凋亡增加,细胞周期停滞在 S 期。HCPT 治疗可抑制体内黑色素瘤肺转移。与静脉或腹腔内给药相比,经雾化吸入给予 HCPT 可观察到更显著的抑制作用。因此,HCPT 对体外和体内 B16-F10 细胞表现出潜在的抗癌活性。然而,仍需要进一步研究可能涉及的机制来解释这种行为。