Peroxiredoxin 2 调控自噬在结直肠癌5-氟尿嘧啶耐药中的作用及机制研究

Chemotherapy resistance is one of the major causes of teatment failure in colorectal cancer (CRC). The previous study found that antioxidant enzymes Peroxiredoxin 2 (Prdx2) is closely related to the chemotherapy drug resistant tumor cells. However, cellular mechanisms underlying the involvement of Prdx2 in chemotherapy drug resistance is still unclear. Our previous findings also preliminary confirmed that Prdx2 expression is significantly up-regulated in chemotherapy resistant colon cancer tissues and cells, and the sensitivity of 5-fluorouracil(5-FU) to CRC cells is increased and the levels of autophagy is decreased significantly after silencing of Prdx2 expression. Therefore, we hypothesized that Prdx2 may play a promoting role in 5-FU drug-resistant CRC cells through regulating autophagy. The present study is going to detect Prdx2 differential expression in tumor tissues of CRC patients before and after drug resistance, explore the regulatory effect of Prdx2 on autophagy and the related biological characteristics in 5-FU drug-resistant CRC cells. We are also going to investigate specific mechanisms underlying the involvement of regulation of autophagy by Prdx2 in 5-FU resistance CRC cells, and in order to clarify the role of Prdx2 and the specific mechanism in CRC chemotherapy resistance. The project will offer a new breakthrough point for the individualized treatment of CRC patients.

肿瘤细胞化疗耐药是影响结直肠癌（CRC）治疗效果的主要原因之一。研究发现Peroxiredoxin 2（Prdx2）与肿瘤细胞化疗耐药密切相关，但Prdx2在CRC化疗耐药中的作用及具体机制尚不明确。我们的前期研究发现Prdx2在化疗耐药的结肠癌组织和细胞中表达上调，抑制Prdx2的表达能够明显增加结肠癌耐药细胞对5-氟尿嘧啶（5-FU）的敏感性，并能显著降低结肠癌耐药细胞的自噬水平。因此，本项目提出假说：Prdx2可能通过调控细胞自噬在CRC细胞5-FU耐药中起促进作用。本研究拟通过检测CRC患者耐药前后肿瘤组织中Prdx2的表达情况，探讨Prdx2对5-FU耐药的CRC细胞自噬的调控作用及其相关生物学特性的影响，进一步探寻Prdx2调控自噬影响CRC细胞5-FU敏感性的相关机制，以期阐明Prdx2在CRC化疗耐药中的作用及具体机制。本课题的开展将为CRC的个体化治疗提供新的切入点。