洛铂对人卵巢癌荷瘤裸鼠存活期的影响

Effect of lobaplatin on the survival time of nude mice bearing human ovarian cancer cells

目的提供洛铂(LBP)治疗卵巢癌的体内药效学证据。方法分别于裸小鼠腹腔接种人卵巢癌SW626、A2780、顺铂(DDP)耐药SK-OV-3细胞,以国际标准一线治疗药物DDP、卡铂(CBP)为对照,系统评价LBP单药或联合紫杉醇(PTX)、多西他赛(TXT)对人卵巢癌荷瘤裸鼠的存活期影响。结果接种SW626细胞各组裸小鼠中位生存时间、第47日存活率:LBP组(3.75、7.5、15 mg·kg-1,IP)分别为42.5、42、45.5 d和13%、25%、50%;DDP组(5 mg·kg-1,IP)为>47 d、75%;CBP组(60 mg·kg-1,IP)分别为>47 d、63%;对照组仅为29 d、17%。接种A2780细胞(D3给药)各组裸小鼠第52日的存活率均为100%,对照组仅为16.7%。接种A2780细胞(D8给药)各组裸小鼠生存时间、第42日存活率:LBP组(3.75、7.5 mg·kg-1,IP)分别为35、36 d和25%、25%;DDP(5 mg·kg-1,IP)为38 d、38%;CBP组(60mg·kg-1,IP)为>35.5 d、13%;对照组为34.5 d、0%。接种DDP耐药SK-OV-3细胞裸小鼠各组中位生存时间、第28日存活率:LBP组(3.75、7.5、15 mg·kg-1,IP)分别为22、27、>28 d和0%、13%、75%;DDP组(5 mg·kg-1,IP)为24 d,38%;CBP组(60 mg·kg-1,IP)为>25.5 d,38%;对照组为22 d,33%。接种DDP耐药SK-OV-3细胞小鼠的第28日存活率、生存延长率:单药TXT(10 mg·kg-1,IV)组为12.5%、21%,LBP(7.5 mg·kg-1,IP)联合TXT(10 mg·kg-1,IV)组为62.5%、53%,单药LBP(7.5 mg·kg-1,IP)、单药CBP(30 mg·kg-1,IP)、单药PTX(10 mg·kg-1,IV)及其他联合用药组第28日均无生存。结论 LBP治疗卵巢癌的疗效与DDP、CBP相当,对DDP耐药型卵巢癌依然有效,其中LBP联合TXT具有明显协同抗肿瘤作用。

Objective To provide pharmacodynamic evidence for the effect of lobaplatin（LBP） on ovarian cancer in vivo. Methods Human ovarian carcinoma SW626, A2780, and SK-OV-3 cells were inoculated intraperitoneally to nude mice, to evaluate the influence of LBP alone or combined with paclitaxel（PTX） and docetaxel（TXT） on the survival time of nude mice bearing SW626, A2780, and SK-OV-3 cells compared with cisplatin（DDP） and carboplatin（CBP）. Results The median survival time and survival rate（D47） of nude mice bearing SW626 cells in each group were as follows： 42.5, 42, and 45.5 days, 13%, 25%, and 50%（the LBP groups of 3.75, 7.5, and 15 mg·kg^- 1, IP）; 〉47 days,75%（the DDP group 5 mg·kg^- 1, IP）; 〉47 days and 63%（the CBP group 60 mg·kg^- 1, IP; 29 days, 17% the control group, IP）. The survival rate（D52） of nude mice bearing A2780 cells（D3 treatment） was 100% in each group while only 16.7% in the control group. The median survival time and survival rate（D42） of nude mice bearing A2780 cells（D8 treatment） in each group were as follows： 35 and 36 days; 25% and 25%（the LBP groups of 3.75 and 7.5 mg·kg^- 1, IP）; 38 days, 38%（the DDP group 5 mg·kg^- 1, IP）; 〉35.5 days, 13%（the CBP group 60 mg·kg^- 1, IP）;34.5 days, 0%（the control group）. The median survival time and survival rates（D28） of nude mice bearing DDP-resistant SK-OV-3 cells： 22, 27, 〉28 days, 0%, 13%, 75%（the LBP groups of 3.75, 7.5 and 15 mg·kg^- 1, IP）; 24 days, 38%（the DDP group 5mg·kg^- 1, IP）; 〉25.5 days, 38%（the CBP group 60 mg·kg^- 1, IP）; 22 days, 33%（the control group）. The survival rates（D28） and rates of prolonging survival time of nude mice bearing DDP-resistant SK-OV-3 cells： 12.5% and 21%（the TXT group 10 mg·kg^-1,IV）, 62.5%, 53% [LBP（7.5 mg·kg^- 1, IP） combined TXT（10 mg·kg^- 1） group, IV]. The survival rates（D28） of the LBP（7.5 mg·kg^- 1, IP） group, the CBP（30 mg·kg^- 1, IP） group, PTX（10 mg·kg^- 1, IV） group and the other groups of combination therapy were 0%. Conclusion The effect of LBP on DDP-sensitive ovarian cancer is similar to that of DDP and CBP. The treatment of LBP on DDP-resistant ovarian cancer is effective, especially LBP in combination with TXT shows synergistically anti-tumor effect, indicating potential clinical advantages of LBP on ovarian cancer.