Hernández-Luna Marco Antonio, Díaz de León-Ortega Ricardo, Hernández-Cueto Daniel Dimitri, Gaxiola-Centeno Ricardo, Castro-Luna Raúl, Martínez-Cristóbal Leonel, Huerta-Yépez Sara, Luria-Pérez Rosendo
Departamento de Medicina y Nutrición, División Ciencias de la Salud, Universidad de Guanajuato Campus Léon, León, Guanajuato, Mexico.
Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
Bol Med Hosp Infant Mex. 2016 Nov-Dec;73(6):388-396. doi: 10.1016/j.bmhimx.2016.10.002. Epub 2016 Dec 1.
Tumor cell resistance to chemotherapy agents is one of the main problems in the eradication of different neoplasias. One of the mechanisms of this process is the overexpression of anti-apoptotic proteins such as Bcl-2 and Bcl-; blocking the activity of these proteins may contribute to the sensitization of tumor cells and allow the adequate effects of chemotherapeutic drugs.
This study adressed the transfection of prostate cancer cells (PC3) with a plasmid encoding a recombinant protein with an antagonist peptide from the BH3 region of the Bax protein fused to the GFP reporter protein (BaxGFP). This protein induced apoptosis of these tumor cells; further, selective transport of this plasmid to the tumor cell with Salmonella enterica serovar Typhimurium (strain SL3261), a live-attenuated bacterial vector, can induce sensitization of the tumor cell to the action of drugs such as cisplatin, through a process known as bactofection.
These results suggest that Salmonella enterica can be used as a carrier vector of nucleotide sequences encoding heterologous molecules used in antitumor therapy.
肿瘤细胞对化疗药物的耐药性是根除不同肿瘤的主要问题之一。这一过程的机制之一是抗凋亡蛋白如Bcl-2和Bcl-的过度表达;阻断这些蛋白的活性可能有助于肿瘤细胞的致敏,并使化疗药物产生充分疗效。
本研究探讨了用一种质粒转染前列腺癌细胞(PC3),该质粒编码一种重组蛋白,其含有与绿色荧光蛋白(GFP)报告蛋白融合的来自Bax蛋白BH3区域的拮抗肽(BaxGFP)。这种蛋白诱导这些肿瘤细胞凋亡;此外,利用减毒活细菌载体鼠伤寒沙门氏菌(菌株SL3261)将该质粒选择性转运至肿瘤细胞,可通过一种称为细菌转染的过程诱导肿瘤细胞对顺铂等药物的作用产生致敏。
这些结果表明,鼠伤寒沙门氏菌可作为编码用于抗肿瘤治疗的异源分子的核苷酸序列的载体。