Department of Plastic and Reconstructive Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Ba-Da-Chu Road 33#, Beijing, 100144, People's Republic of China.
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Ba-Da-Chu Road 33#, Beijing, 100144, People's Republic of China.
BMC Cancer. 2019 Sep 14;19(1):921. doi: 10.1186/s12885-019-6111-5.
Free flap-mediated gene therapy in the tumor bed following surgical resection is a promising approach in cancer targeted treatment of residual disease. We investigated the selective killing efficacy of a lentivirus-mediated cytosine deaminase-thymidine kinase (CDglyTK) gene in transplanted breast cancer delivered into a free flap by intra-artery perfusion.
Proliferation, apoptosis, and cell cycle of rat SHZ-88 breast cancer cells transfected with a lentivirus-mediated CD/TK gene were measured following treatment with ganciclovir and 5-flucytosine in vitro. A model of residual disease of breast cancer in a rat superficial inferior epigastric artery (SIEA) flap model was used to study the therapeutic potential of a double suicide CD/TK and prodrug system in vivo.
Killing efficacy of the double suicide CD/TK and prodrug system on SHZ-88 cells was mediated by increased apoptosis and cell cycle arrest at the G1 phase with significant bystander effect. Following recombinant lentivirus transfection of rat SIEA flap by intra-artery perfusion, CD/TK gene expression was limited to the flap, and the volume and weight of transplanted tumors were significantly reduced without observable toxicity.
SIEA flaps transfected with a lentivirus-mediated CDglyTK gene by intra-artery perfusion effectively suppress transplanted breast tumor growth without obvious systemic toxic effects in rats.
游离皮瓣介导的基因治疗是肿瘤床切除术后肿瘤靶向治疗残余疾病的一种很有前途的方法。我们研究了通过动脉内灌注将携带胞嘧啶脱氨酶-胸苷激酶（CDglyTK）基因的慢病毒转染入游离皮瓣中，对种植性乳腺癌的选择性杀伤作用。
在体外通过更昔洛韦和 5-氟胞嘧啶处理转染了慢病毒介导的 CD/TK 基因的大鼠 SHZ-88 乳腺癌细胞，检测其增殖、凋亡和细胞周期。利用大鼠腹壁下动脉（SIEA）皮瓣模型中的乳腺癌残余疾病模型，研究双重自杀 CD/TK 和前药系统在体内的治疗潜力。
双重自杀 CD/TK 和前药系统对 SHZ-88 细胞的杀伤作用是通过增加细胞凋亡和 G1 期细胞周期阻滞介导的，具有显著的旁观者效应。通过动脉内灌注将重组慢病毒转染至大鼠 SIEA 皮瓣后，CD/TK 基因表达仅限于皮瓣，且移植瘤的体积和重量明显减少，无明显毒性。
通过动脉内灌注携带慢病毒介导的 CDglyTK 基因的 SIEA 皮瓣可有效抑制大鼠种植性乳腺癌的生长，且无明显的全身毒性作用。
