Caffrey Paula B, Frenkel Gerald D, McAndrew Kathryn L, Marks Kenneth
Department of Biological and Environmental Sciences, California University of PA, California, PA, U.S.A.
Department of Biological Sciences, Rutgers University, Newark, NJ, U.S.A.
In Vivo. 2016;30(6):745-749. doi: 10.21873/invivo.10990.
BACKGROUND/AIM: To study the prevention of chemotherapy resistance, we have previously designed models of drug-resistant ovarian cancer. We here report an in vivo model of cisplatin-resistant small cell lung cancer (SCLC).
Mice bearing H526 SCLC xenografts received intraperitoneal pretreatment with a sub-effective cisplatin dose (0.75-1.5 mg/kg) or no pretreatment (controls). Seven days later, all mice received a higher cisplatin dose (3.0 mg/kg), and tumor response was recorded. Cell cultures initiated from pretreated and control xenografts were tested for cisplatin resistance and for glutathione-S-transferase (GST) activity.
Pretreatment with 1.5 mg/kg cisplatin induced resistance to 3.0 mg/kg cisplatin. Cells from a pretreated tumor were cisplatin resistant and had nearly twice the GST activity as cells from a control tumor.
Such cells may prove useful for identifying other resistance mechanisms and thus guide the selection of potential preventative agents to be tested in the in vivo model.
背景/目的:为研究化疗耐药的预防,我们之前设计了耐药性卵巢癌模型。在此我们报告一种顺铂耐药性小细胞肺癌(SCLC)的体内模型。
携带H526 SCLC异种移植瘤的小鼠接受腹腔内亚有效顺铂剂量(0.75 - 1.5 mg/kg)预处理或不进行预处理(对照组)。7天后,所有小鼠接受更高剂量的顺铂(3.0 mg/kg),并记录肿瘤反应。对来自预处理和对照异种移植瘤的细胞培养物进行顺铂耐药性和谷胱甘肽 - S - 转移酶(GST)活性检测。
1.5 mg/kg顺铂预处理诱导了对3.0 mg/kg顺铂的耐药性。来自预处理肿瘤的细胞对顺铂耐药,其GST活性几乎是来自对照肿瘤细胞的两倍。
这类细胞可能有助于识别其他耐药机制,从而指导在体内模型中测试潜在预防药物的选择。