Rabzia Arezou, Khazaei Mozafar, Rashidi Zahra, Khazaei Mohammad Rasoul
Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Iran J Pharm Res. 2017 Fall;16(4):1432-1442.
Paclitaxel is one of the most common chemotherapeutic drugs used for the treatment of prostate cancer. However, its current clinical utility has been limited due to numerous serious side effects and drug resistance. Noscapine is an antitussive opium alkaloid that showed antitumor activity against a variety of cancer while it has not exhibited severe side effects. This study investigates the anticancer activity of noscapine in combination with paclitaxel against two LNCaP and PC-3 human prostate cancer cell lines LNCaP and PC-3 cells were treated with noscapine or paclitaxel or combination. Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) test. Apoptosis was assessed by acridine orange/ ethidium bromide (AO/EB) staining. The mRNA expression of , , and in the cellular response to treatments was investigated. MTT assay indicated the combination treatment of paclitaxel and noscapine significantly decreased viability compared to single-agent treatment and control groups. The results obtained with AO/EB double staining showed increased percentages of apoptotic cells in the presence of the combination of paclitaxel and noscapine. Furthermore, combinational treatment of paclitaxel and noscapine showed significant decrease in the mRNA expression of B-cell CLL/Lymphoma () and increase in the mRNA expression of Bcl-2-associated X protein (( and / ratio in LNCaP and PC-3 cells (<0.05.( The mRNA expression of androgen receptor ) and prostate specific antigen () decreased in paclitaxel and noscapine combination-treated of LNCaP cells (<0.05). This study provides a novel concept of combination treatment of paclitaxel and noscapine to improve efficiency in human prostate cancer treatment.
紫杉醇是用于治疗前列腺癌的最常见化疗药物之一。然而,由于众多严重的副作用和耐药性,其目前的临床应用受到限制。那可丁是一种镇咳鸦片生物碱,对多种癌症显示出抗肿瘤活性,同时未表现出严重的副作用。本研究调查了那可丁与紫杉醇联合对两种人前列腺癌细胞系LNCaP和PC-3的抗癌活性。LNCaP和PC-3细胞用那可丁或紫杉醇或联合用药处理。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)试验测定细胞活力。通过吖啶橙/溴化乙锭(AO/EB)染色评估细胞凋亡。研究了在细胞对治疗的反应中,、、和的mRNA表达。MTT分析表明,与单药治疗组和对照组相比,紫杉醇和那可丁联合治疗显著降低了细胞活力。AO/EB双重染色结果显示,在紫杉醇和那可丁联合存在的情况下,凋亡细胞百分比增加。此外,紫杉醇和那可丁联合治疗显示B细胞淋巴瘤()的mRNA表达显著降低,而Bcl-2相关X蛋白(,LNCaP和PC-3细胞中的/比值)的mRNA表达增加(<0.05)。在LNCaP细胞中,紫杉醇和那可丁联合处理后雄激素受体()和前列腺特异性抗原()的mRNA表达降低(<0.05)。本研究为紫杉醇和那可丁联合治疗提供了一个新的概念,以提高人类前列腺癌治疗的效率。