Au J L, Kalns J, Gan Y, Wientjes M G
Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus 43210, USA.
Cancer Chemother Pharmacol. 1997;41(1):69-74. doi: 10.1007/s002800050709.
The goal of this study was to determine whether paclitaxel, when given by a 2-h treatment, produces significant cytotoxic effects in human bladder transitional cell carcinoma and hence qualifies as a candidate drug for intravesical treatment.
Histocultures of surgical specimens from patients (n = 16) were used.
Paclitaxel produced partial inhibition of DNA precursor incorporation in about 70% of tumors and induced apoptosis in about 90% of tumors, while these effects were minimal or not detectable in the remaining tumors. In the responsive tumors, the average maximal inhibition of DNA synthesis was 60% and the average maximal apoptotic index was 15%. Resistance to antiproliferative and apoptotic effects was not always found in the same individual tumors, and no relationship was found between the magnitude of antiproliferative and apoptotic effects in individual tumors. The maximal apoptotic index correlated with the LI for the untreated control (r2 = 0.42, P < 0.01). More than 95% of apoptotic cells were labeled by DNA precursor, whereas not all labeled cells were apoptotic. The pharmacologic effects of paclitaxel in bladder tumors were qualitatively equivalent to those previously found in human head and neck tumors and in human prostate tumors after treatment for longer periods of 24 to 96 h.
These results indicate that a 2-h paclitaxel treatment was sufficient to produce antiproliferation and apoptosis in 70-90% of human bladder tumors, and the apoptotic effect appeared to be linked to proliferation and occurred after DNA synthesis.
本研究的目的是确定紫杉醇在2小时治疗时是否对人膀胱移行细胞癌产生显著的细胞毒性作用，从而使其有资格作为膀胱内治疗的候选药物。
使用了来自患者（n = 16）手术标本的组织培养物。
紫杉醇在约70%的肿瘤中产生了对DNA前体掺入的部分抑制，并在约90%的肿瘤中诱导了凋亡，而在其余肿瘤中这些作用最小或无法检测到。在有反应的肿瘤中，DNA合成的平均最大抑制率为60%，平均最大凋亡指数为15%。对增殖抑制和凋亡作用的抗性并非总是在同一肿瘤个体中出现，且在个体肿瘤中增殖抑制和凋亡作用的大小之间未发现相关性。最大凋亡指数与未处理对照的LI相关（r2 = 0.42，P < 0.01）。超过95%的凋亡细胞被DNA前体标记，而并非所有被标记的细胞都是凋亡细胞。紫杉醇在膀胱肿瘤中的药理作用在质量上与先前在人头颈肿瘤和人前列腺肿瘤中经过24至96小时更长时间治疗后发现的作用相当。
这些结果表明，2小时的紫杉醇治疗足以在70 - 90%的人膀胱肿瘤中产生抗增殖和凋亡作用，且凋亡作用似乎与增殖相关并在DNA合成后发生。
