Ye Weiping, Chang Hsiang-Lin, Wang Li-Shu, Huang Yi-Wen, Shu Sherry, Dowd Michael K, Wan Peter J, Sugimoto Yasuro, Lin Young C
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210-1092, USA.
Anticancer Res. 2007 Jan-Feb;27(1A):107-16.
Multidrug resistance (MDR) is a major impediment to successful cancer chemotherapy. P-glycoprotein (P-gp), the product of the multidrug resistance 1 (MDR1) gene, acts as an efflux pump and prevents sufficient intracellular accumulation of several anticancer agents, thus, playing a major role in MDR. Tamoxifen (Tam), ICI 182 780 (ICI) and Adriamycin (Adr) alone or with (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] possible effects on cell growth inhibition and regulation of MDR1, mRNA and P-gp expression were examined in both an MDR human breast cancer cell line, MCF-7/Adr cells, and primary cultured human breast cancer epithelial cells (PCHBCEC).
Cells were treated with 0.05% of (-)-GPCSO either in the absence or presence of either 0.1 microM Tam, ICI or Adr for 24 h.
Using the non-radioactive cell proliferation MTS assay, none of these chemotherapeutic agents alone inhibited MCF-7/Adr cell and PCHBCEC proliferation; meanwhile, the combination of 0.1 microM Tam, ICI or Adr with 0.05% (-)-GPCSO significantly reduced MCF-7/Adr cell growth by approximately 34%, 32% and 23%, respectively, of that of the vehicle-treated cells. For PCHBCEC, the combination of 0.05% (-)-GPCSO with 0.1 microM of Tam, ICI and Adr reduced cell growth to about 94%, 90%, and 71% respectively, of the vehicle treated PCHBCEC. Furthermore, (-)-GPCSO inhibited MDR1/P-gp expression in both MCF- 7/Adr and PCHBCEC in a dose-dependent manner. Our results provide insight into the MDR-reversing potential of (-)-GPCSO in human breast cancer cells resistant to current chemotherapeutic agents.
多药耐药性（MDR）是癌症化疗成功的主要障碍。多药耐药 1（MDR1）基因的产物 P-糖蛋白（P-gp）作为一种外排泵，可阻止多种抗癌药物在细胞内充分蓄积，因此在多药耐药中起主要作用。在多药耐药的人乳腺癌细胞系 MCF-7/Adr 细胞和原代培养的人乳腺癌上皮细胞（PCHBCEC）中，研究了他莫昔芬（Tam）、ICI 182 780（ICI）和阿霉素（Adr）单独或与富含（-）-棉酚的棉籽油[（-）-GPCSO]联合使用对细胞生长抑制以及 MDR1、mRNA 和 P-gp 表达调控的可能影响。
细胞在不存在或存在 0.1μM Tam、ICI 或 Adr 的情况下，用 0.05%的（-）-GPCSO 处理 24 小时。
使用非放射性细胞增殖 MTS 试验，这些化疗药物单独使用均未抑制 MCF-7/Adr 细胞和 PCHBCEC 的增殖；同时，0.1μM Tam、ICI 或 Adr 与 0.05%（-）-GPCSO 联合使用分别使 MCF-7/Adr 细胞生长显著降低约 34%、32%和 23%，与溶媒处理的细胞相比。对于 PCHBCEC，0.05%（-）-GPCSO 与 0.1μM 的 Tam、ICI 和 Adr 联合使用分别使细胞生长降低至溶媒处理的 PCHBCEC 的约 94%、90%和 71%。此外，（-）-GPCSO 以剂量依赖性方式抑制 MCF-7/Adr 和 PCHBCEC 中 MDR1/P-gp 的表达。我们的结果为（-）-GPCSO 在对当前化疗药物耐药的人乳腺癌细胞中的多药耐药逆转潜力提供了见解。
