Bactofection of sequences encoding a Bax protein peptide chemosensitizes prostate cancer tumor cells

Marco Antonio Hernández-Luna , Ricardo Díaz de León-Ortega , Daniel Dimitri Hernández-Cueto , Ricardo Gaxiola-Centeno , Raúl Castro-Luna , Leonel Martínez-Cristóbal , Sara Huerta-Yépez , Rosendo Luria-Pérez
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引用次数: 2

Abstract

Background

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-XL; blocking the activity of these proteins may contribute to the sensitization of tumor cells and allow the adequate effects of chemotherapeutic drugs.

Methods and results

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.

Conclusions

These results suggest that Salmonella enterica can be used as a carrier vector of nucleotide sequences encoding heterologous molecules used in antitumor therapy.

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细菌感染编码Bax蛋白肽的序列可使前列腺癌肿瘤细胞化学致敏
肿瘤细胞对化疗药物的耐药性是各种肿瘤根治的主要问题之一。这一过程的机制之一是抗凋亡蛋白如Bcl-2和Bcl-XL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,并使化疗药物发挥充分的作用。方法和结果本研究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,其中Bax蛋白BH3区域的拮抗剂肽与GFP报告蛋白(BaxGFP)融合。该蛋白诱导肿瘤细胞凋亡;此外,用肠炎沙门氏菌血清型鼠伤寒沙门氏菌(SL3261菌株)(一种减毒活细菌载体)选择性地将这种质粒转运到肿瘤细胞中,可以通过一个被称为细菌感染的过程诱导肿瘤细胞对顺铂等药物的作用致敏。结论肠沙门氏菌可作为异源分子核苷酸序列的载体,用于抗肿瘤治疗。
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