PO.ET09.08 · 实验与分子治疗

NAD(P)H:醌氧化还原酶1（NQO1）：它是结直肠癌中潜在的分子靶点吗？

NAD(P)H: Quinone oxidoreductase 1 (NQO1): Is it a potential molecular target in colorectal cancer?

编号 7088 展板 8 时间 4/22 09:00–12:00 区域 Section 13 主讲 Chaithanya Ganji, No Degree

分会场 Novel Antitumor Agents 3

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作者与单位 Authors & Affiliations

Chaithanya Ganji¹, Raasil R. Basha², Karthikeya Ganji³, Mehmet Akce⁴, Bassel F. El-Rayes⁵

¹Hematology and Oncology, O'Neal Comprehensive Cancer Center at UAB, Birmingham, AL,²Missouri Southern State University, Fort Worth, TX,³Harrison High School, Kennesaw, GA,⁴University of Alabama at Birmingham, Birmingham, AL,⁵University of California San Diego, La Jolla, CA

摘要 Abstract

中文摘要

背景：结直肠癌（CRC）是美国第三大最常见的癌症，与不良预后相关。NAD(P)H:醌氧化还原酶1（NQO1）是一种已被证明有助于CRC化学保护的酶。本meta分析的目的是研究NQO1 C609T多态性与CRC风险之间的关系。本研究还使用分子对接研究了BBI 608对CRC中NQO1的结合能力和疗效。方法：使用Google Scholar、PubMed和Web of Science进行文献检索。NQO1 C609T分析纳入了18项研究。收集数据后使用合并优势比（OR）及95%置信区间进行计算。使用分子对接、Western Blot和QRT-PCR来确定BBI 608和NQO1的分子功能。结果：NQO1多态性与CRC风险显著相关（OR = 1.19，95% CI = 1.06-1.34，p < 0.001）。按种族进行的分层检查发现NQO1多态性与CRC风险之间存在显著关联（TT + CT vs. CC：OR = 1.17，95% CI = 1.08-1.27，p < 0.001）。本研究表明NQO1 C609T多态性会增加亚洲人和白种人的CRC风险。使用计算技术探索BBI 608（一种NQO1抑制剂）的分子特征，并确定NQO1在CRC中的精确机制。本研究深入洞察了NQO1与BBI 608之间的相互作用及其对CRC治疗的意义。进行了体外实验以补充这一计算分析。BBI 608在CRC细胞系中引起剂量依赖性细胞毒性。BBI 608治疗在两种CRC细胞系（HCT116和RKO）中均显著（p < 0.001）降低了NQO1在蛋白质和RNA水平上的表达。结论：根据meta分析和计算技术，NQO1是CRC中一个有效的生物标志物和可能的分子靶点。体外研究表明，用BBI 608抑制NQO1可减少两种CRC细胞系的细胞生长。敲除、过表达和定点诱变对于更深入理解BBI 608靶向的NQO1及其氨基酸残基是必要的。

查看英文原文 English abstract

Background: Colorectal cancer (CRC) is the third most frequent cancer in the United States, and it is linked to poor outcomes. NAD(P)H: Quinone Oxidoreductase 1 (NQO1) is an enzyme that has been demonstrated to help in chemoprotection in CRC. The purpose of this meta-analysis is to investigate the relationship between NQO1 C609T polymorphisms and the risk of CRC. The study also investigates the binding ability and efficacy of BBI 608 against NQO1 in CRC using molecular docking. Methods: Google Scholar, PubMed, and Web of Science were utilized for bibliographic searches. The NQO1 C609T analysis included 18 studies. Data was collected and then calculated using the pooled odds ratio (OR) with a 95% confidence interval. Molecular docking, Western Blot, and QRT-PCR were utilized to determine BBI 608 and NQO1's molecular function. Results: The NQO1 polymorphism was significantly associated with CRC risk (OR = 1.19, 95% CI = 1.06-1.34, p < 0.001). A stratified examination by ethnicity found a significant connection between the NQO1 polymorphism and CRC risk (TT + CT vs. CC: OR = 1.17, 95% CI = 1.08-1.27, p < 0.001). This study demonstrates that the NQO1 C609T polymorphism increases the risk of CRC in both Asians and Caucasians. Computational techniques were used to explore the molecular characteristics of BBI 608 (an NQO1 inhibitor) and determine the precise mechanism of NQO1 in CRC. This study provides a deep insight into the interplay between NQO1 and BBI 608, as well as its implications for CRC treatment. In vitro experiments were conducted to supplement this computational analysis. BBI 608 causes dose-dependent cytotoxicity in CRC cell lines. BBI 608 treatment significantly ( p < 0.001) decreased NQO1 expression at protein and RNA levels in both CRC cell lines (HCT116 and RKO). Conclusion: According to a meta-analysis and computational technique, NQO1 is a valid biomarker and possible molecular target in CRC. In vitro studies revealed that suppressing NQO1 with BBI 608 reduced cell growth in both CRC cell lines. Knockout, overexpression, and site-directed mutagenesis are necessary for a deeper understanding of BBI 608-targeted NQO1 and its amino acid residues.

利益披露 Disclosure

C. Ganji, None.. K. Ganji, None.

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