注射用多西他赛磺丁基-β-环糊精包合物的体外抗肿瘤作用

In vitro antitumor effect of the sulfobutyl-β-cyclodextrin inclusion of docetaxel for injection

为了评价注射用多西他赛磺丁基-β-环糊精包合物(ML061)对各种体外培养肿瘤细胞的细胞毒性作用,本研究选取MDA-MB-435、MDA-MB-435s、NCI-H446、HO-8910、Bcap-37、KB、SMMC-7721、HT-29、SW480、LS-174t、SGC-7901、MCF-7、A549、NCI-H460等14个肿瘤细胞株,分别用不同质量浓度(200,20,2,0.2,0.02,0.002,0.000 2,0.000 02μg/mL)ML061处理肿瘤细胞72 h,用MTT法测定细胞活力,并计算药物对各肿瘤细胞的半数抑制浓度IC50。结果发现,ML061可抑制多种体外培养的肿瘤细胞株的活力,且这种抑制作用呈剂量依赖性。与阳性对照药市售多西他赛注射液奥名润相比,在选取的14个肿瘤细胞株中,ML061对Bcap-37、MDA-MB-435、MDA-MB-435s、NCI-H446和SW480的IC50小于0.1μg/mL。ML061对人卵巢癌Bcap-37、人结肠癌SW480、人小细胞肺癌NCI-H446、人乳腺癌MDA-MB-435及MDA-MB-435s等肿瘤细胞株的体外抑制作用较强。总之,ML061抑制多种体外培养的肿瘤细胞增殖,与阳性对照药奥名润相同,以Bcap-37、SW480、NCI-H446和MDA-MB-435s这4个细胞株较为敏感,而MDA-MB-435对ML061的敏感性高于奥名润。

To evaluate the in vitro cytotoxicity of the sulfobutyl-β-cyclodextrin inclusion of docetaxel for injection （ML061） on various tumor cell lines, 14 tumor cell lines including MDA-MB-435, MDA-MB-435s, NCI-H446, HO-8910, Bcap-37, KB, SMMC-7721, HT-29, SW480, LS-174t, SGC-7901, MCF-7, A549 and NCI-H460 were used for the treatment with ML061 at different concentrations （200, 20, 2, 0. 2, 0. 02, 0. 002, 0. 000 2, 0. 000 02 txg/mL） for 72 h, then the cell proliferation was evaluated by MTT method, and finally ICso was calculated. It was found that ML061 selectively inhibited the proliferation of a variety of tumor cell lines in vitro, with a certain in vitro killing effect on the 14 tumor cell lines in a dose-dependent trend. It was found that among the 14 tumor cell lines, the IC50 values of Bcap-37, MDA-MB-435, MDA-MB-435s, NCI-H446 and SW480 were less than 0. 1 μg,/mL（ being sensitive to ML061）. Compared with the positive control Aomingrun, ML061 had stronger in vitro inhibition effect on human ovarian cancer Bcap-37, human colon cancer SW480, human small cell lung cancer NCI-H446, human breast cancer MDA-MB-435 and MDA-MB-435s. In conclusion, ML061 inhibits the proliferation of a variety of tumor cell lines in vitro, of which Bcap-37, SW480, NCI-H446 and MDA-MB-435s cell lines are as sensitive as Aomingrun, but MDA-MB-435 is more sensitive to ML061 than Aomingrun.