Increased efficiency of cisplatin-resistant cell lines to DNA-mediated gene transfer with cationic liposome
Increased efficiency of cisplatin-resistant cell lines to DNA-mediated gene transfer with cationic liposome
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DOI：
10.1111/j.1447-0756.2005.00304.x
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发表时间：
2005-01-01
影响因子：
1.6
通讯作者：
Tanaka, K
中科院分区：
文献类型：
--
作者：
Sato, T;Serikawa, T;Tanaka, K
目的：由于其对许多妇科恶性肿瘤的有效性，包括顺铂在内的化疗主要用作上皮性卵巢癌的一线化疗。然而，公认的主要问题之一是肿瘤细胞可以容易地获得对顺铂的抗性。为了建立针对顺铂耐药肿瘤细胞的治疗方法，进行了各种试验。方法：使用体内和体外研究，我们检查了新开发的脂质体是否可以用作顺铂耐药肿瘤细胞的抗癌试剂来证明足够的转染活性。用我们新开发的脂质体，GTE 319和GTE 321，lac-Z基因更有效地转染顺铂耐药变异细胞，mEIIL-R，KF-ra和KF-rb，比亲本细胞，mEIIL和KF，使用X-gal染色。在细胞毒实验中，转染单纯疱疹胸苷激酶（HSV-tk）基因的GTE 319或GTE 321偶联物，与阿昔洛韦共同培养5天后，发现所有顺铂耐药的肿瘤细胞的抑瘤活性均比未处理的亲本细胞的抑瘤活性增强。此外，高的抗肿瘤效果是从肿瘤内局部注射的tk基因与GTE-321脂质体共轭阿昔洛韦管理后，对KF-Rb移植瘤形成在裸鼠hypodermic.Conclusion：这些结果表明，使用新开发的脂质体共轭自杀基因的基因治疗可以是一个有吸引力的方法对顺铂耐药的卵巢癌细胞的治疗。
Aim: Because of its effectiveness against many gynecologic malignancies, chemotherapy including cisplatin is mainly used as the first-line chemotherapy for epithelium ovarian cancer. However, one of the major problems that is well recognized is that tumor cells can easily acquire resistance to cisplatin. Various trials were carried out in order to establish treatment against cisplatin-resistant tumor cells.Method: Using both in vivo and in vitro studies, we examined whether or not the newly developed liposome could be used to demonstrate sufficient transfection activity as the anticancer reagent for cisplatin-resistant tumor cells.Result: With our newly developed liposome, GTE 319 and GTE 321, the lac-Z gene was more efficiently transfected in cisplatin-resistant variant cells, mEIIL-R, KF-ra and KF-rb, than in parental cells, mEIIL and KF, using X-gal staining. In cytotoxic assay, transfection of herpes simplex thymidine kinase (HSV-tk) gene conjugated with GTE319 or GTE 321, and cultivation with aciclovir for 5 days revealed accelerated tumor-inhibition activity in all of the cisplatin-resistant tumor cells compared with that in the naive parental cells. In addition, the high anti-tumor effect was obtained from intratumoral local injection of the tk gene conjugated with GTE-321 liposome following aciclovir administration against KF-rb-transplanted tumor formed in nude mouse hypodermic.Conclusion: These results suggest that gene therapy using a newly developed liposome-conjugated suicide gene can be an attractive approach for treatment against cisplatin-resistant ovarian cancer cells.