In Vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Malignant Melanoma
In Vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Malignant Melanoma
复制标题
重组人腺病毒-p53注射液治疗恶性黑色素瘤的体外和临床研究
DOI：
10.1089/humc.2018.112
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发表时间：
2019
影响因子：
--
通讯作者：
Yi Li
中科院分区：
文献类型：
--
作者：
Shanwei Shi;Bo Li;Yang Dong;Yang Ge;Xing Qu;Liguang Lu;Yihang Yuan;Longjiang Li;Yi Li
Malignant melanoma is an aggressive tumor with high fatality rates and poor prognosis, mainly due to the lack of efficient treatment methods. The present study investigated the potential antitumor effects of recombinant adenovirusp53(rAd-p53) on human malignant melanoma. The optimal viral titer on a human malignant melanoma (A-375) cell line was determined for the rAd-p53treatment. The invasive abilities, apoptosis, variations in the cell cycle, and molecular expression levels of A-375 cells were detected after infection by rAd-p53. A tumor growth curve and hematoxylin and eosin staining were carried out for experiments in nude mice. Twenty-one patients with malignant melanoma were evaluated, including 12 cases without gene therapy and nine cases with rAd-p53gene therapy. The overall survival rate and the median survival time were analyzed between the two groups of patients. When the multiplicity of infection was 100, the cells showed the best transfection efficiency. The invasive ability, apoptosis, cycle changes of the cells, and the expression of thep53,p21, andBaxgenes and proteins were significantly changed in the experimental group. In nude mice, the tumor growth curve and the tumor size in the experimental group were significantly smaller than those of the control group. Hematoxylin and eosin staining revealed tumor metastasis in the blank group and the control group but not in the experimental group. Between the two groups of patients, the median survival of the gene therapy group (38 months) was greater than that of the group without gene therapy (27 months). In this study, high expression of thep53gene could regulate the gene expression and reduce the invasive and metastatic abilities of the tumor cells. Furthermore, rAd-p53effectively improved the survival of patients with malignant melanoma. Therefore, rAd-p53may be a potential treatment method for human malignant melanoma.
