羟基喜树碱和topotecan对人卵巢癌细胞株体外作用的研究

目的 观察１０－羟基喜树碱（羟基喜树缄）和９－二甲基氨基－１０羟基喜树缄（ｔｏｐｏｔｅｃａｎ）对卵巢癌细胞株体外生长的影响。方法 采用四甲基偶氮唑蓝（ＭＴＴ）比色法,测定羟基喜树碱和ｔｏｐｏｔｅｃａｎ对卵巢癌细胞株ＳＫＯＶ３和ＣＡＯＶ３生长的抑制作用,并绘制浓度－抑制率曲线,观察这两种药物对ＳＫＯＶ３和ＣＡＯＶ３的生长及集落形成的抑制作用,并与顺铂进行对比;用末端脱氧核酰转移酶介导的脱氧尿苷三磷酸

The effect of hydroxycamptothecin and topotecan to SKOV3 and CAOV3 in vitro

Objective To examine the effect of hydroxycamptothecin (HCPT) and topotecan, two kinds of derivative of camptothecin, to two ovarian cancer cell lines, SKOV3 and CAOV3. Methods Methyl thiazolyl tetrazolium (MTT) was used to establish the dose effect curves. The ability of these two drugs to induce apoptosis of the two cell lines was determined by the method of terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA Ladder. The morphological changes of the cells were observed by electronic microscope. Expression of c myc, bcl 2, and fas was estimated by the immunohistochemical staining. Results The inhibition of HCPT and topotecan to the growth of SKOV3 and CAOV3 was dose dependent. 50% inhibiting concentration (IC50) of HCPT and topotecan to SKOV3 was 72 ng/ml and 160 ng/ml, respectively; IC10 of HCPT and topotecan to CAOV3 was 141 ng/ml and 12 ng/ml, respectively. The inhibition of HCPT and topotecan to clone forming rate of two cell lines was significant. The growing curves of SKOV3 and CAOV3 treated by HCPT and topotecan were significantly lower than controls. HCPT and topotecan of 5 ng/ml can elongate the double time of SKOV3 for 49.00 and 1.75 times, respectively. They can elongate the double time of CAOV3 for 2.77 and 1.94 times, respectively. After treated by HCPT or topotecan, SKOV3 generated DNA Ladder. Positive rates of TUNEL of SKOV3 and CAOV3 were elevated by HCPT and topotecan notably. HCPT and topotecan did not affect the expression of c myc, bcl 2, fas of SKOV3 and CAOV3. Observed by electronic microscope, heterochromatin of SKOV3 and CAOV3 coagulated after treated by HCPT. Micro villi of SKOV3 and CAOV3 were damaged, and some vacuoles appeared in the cytoplasm. Conclusions HCPT and topotecan can inhibit growth of SKOV3 and CAOV3 significantly. HCPT and topotecan can induce apoptosis of SKOV3 and CAOV3.