新型KRAS突变体抑制剂抗胰腺癌的作用研究<sup>★</sup>

doi:10.3969/j.issn.2095-1264.2025.02.04

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新型KRAS突变体抑制剂抗胰腺癌的作用研究★
DOI:
                        10.3969/j.issn.2095-1264.2025.02.04
                    
作者:
                        
                        
                    
作者单位:1.湖南师范大学医学部 小分子靶向药物研究与创制湖南省重点实验室，湖南 长沙，410013;2.湖南九典制药股份有限公司，湖南 长沙，410205
作者简介:罗桂芳，男，硕士研究生，研究方向为肿瘤药效机制研究。
通讯作者:杨小平，男，教授，博士研究生导师，研究方向为肿瘤药理及小分子靶向药物创制。
中图分类号:R735.9;R979.1
基金项目:★湖南师范大学生殖健康与转化医学研究团队资助项目（2023JC101）。

Study on the effects of novel KRAS mutant inhibitors on pancreatic cancer^★

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Affiliation:

1.Key Laboratory of Small Molecule Targeted Drug Research and Development in Hunan Province, Health Science Center,Hunan Normal University, Changsha, 410013, Hunan, China;2.Hunan Jiudian Pharmaceutical Co., Ltd., Changsha, 410205, Hunan, China

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摘要:

目的探究新型KRAS突变体抑制剂JQC系列化合物（JQC-001~JQC-006）对胰腺癌的作用。方法采用MTT法检测JQC系列化合物对KRAS突变型肿瘤细胞（DU 145、A549、PANC-1、HCT-116）增殖的抑制作用；通过RT-qPCR法检测JQC-005对PANC-1细胞KRAS mRNA表达水平的影响；建立PANC-1荷瘤裸鼠模型评估JQC-005的体内抗肿瘤活性。结果除JQC-004外，其余JQC化合物均呈剂量依赖性抑制人前列腺癌DU 145细胞、人非小细胞肺癌A549细胞、人胰腺癌PANC-1细胞、人结肠癌HCT-116细胞的增殖。JQC-005可显著下调PANC-1细胞KRAS mRNA表达，并对PANC-1荷瘤裸鼠肿瘤生长具有明显的抑制作用。结论 JQC系列化合物（特别是JQC-005）具有显著的抗胰腺癌作用，其机制可能与调控KRAS突变体活性相关。

Abstract:

Objective To delineate the effects of the novel KRAS mutant inhibitor JQC series compounds (JQC-001 to JQC-006) on pancreatic cancer.Methods The inhibitory effects of JQC compounds on the proliferation of KRAS-mutant tumor cells (DU 145, A549, PANC-1, HCT-116) were evaluated using the MTT assay. RT-qPCR was performed to assess the impact of JQC-005 on KRAS mRNA expression in PANC-1 cells. A PANC-1 xenograft nude mouse model was established to evaluate the in vivo antitumor activity of JQC-005.Results With the exception of JQC-004, the remaining JQC series compounds (JQC-001, JQC-002, JQC-003, JQC-005, JQC-006) were found to inhibit the proliferation of human prostate cancer DU 145 cells, human non-small cell lung cancer A549 cells, human pancreatic cancer PANC-1 cells, and human colon cancer HCT-116 cells in a dose-dependent manner. JQC-005 significantly down-regulated the expression of KRAS mRNA in PANC-1 cells, and markedly suppressed tumor growth in the PANC-1 xenograft nude mouse model.Conclusion The JQC series compounds, particularly JQC-005, exhibit significant anti-pancreatic cancer effects, potentially mediated through regulation of KRAS mutant activity.