| 引用本文: | 钱炫圳,李玲,吴征宇,黄仕美,王碧,蔡燕.PAFAH1B3通过下调AMPK-ACC通路抑制脂肪酸氧化增强BRAFV600E甲状腺乳头癌细胞对维莫非尼的耐药性[J].中国现代应用药学,2026,43(7):51-58. |
| qianxuanzhen,liling,wuzhengyu,huangshimei,wangbi,caiyan.PAFAH1B3 inhibits fatty acid oxidation by down-regulating the AMPK-ACC pathway to enhance vemurafenib resistance in BRAFV600E papillary thyroid cancer cells[J].Chin J Mod Appl Pharm(中国现代应用药学),2026,43(7):51-58. |
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| 摘要: |
| 摘要：目的 探讨血小板活化因子乙酰水解酶IB3（platelet-activating factor acetylhydrolase IB3，PAFAH1B3）是否可通过调节AMPK-ACC通路促进脂质代谢增强BRAFV600E甲状腺乳头癌细胞对维莫非尼的耐药性。方法 RT-PCR检测细胞中PAFAH1B3的mRNA水平；Western blot检测细胞中PAFAH1B3、Bcl-2、Bax、pAMPK、AMPK、ACC2、pACC相关蛋白水平；油红O染色检测细胞中脂质表达水平；流式细胞术检测细胞凋亡。建立耐药细胞株，通过过表达或敲低，评估PAFAH1B3对其脂质代谢水平的影响。结果 PAFAH1B3在BRAFV600E细胞中表达高于BRAFwt（P<0.05或P<0.001），且在BRAFV600E维莫非尼耐药细胞中PAFAH1B3表达上调（P<0.001）；PAFAH1B3上调可增强细胞对维莫非尼的耐药性，降低细胞的凋亡比例（P<0.05或P<0.01）； OE-PAFAH1B3会降低AMPK磷酸化，从而下调ACC2磷酸化水平，最后显著降低BRAFV600E细胞的脂肪酸氧化水平，增加脂质累积；sh-PAFAH1B3使细胞对维莫非尼敏感性增强，而这种作用会被sh-ACC2逆转。结论 PAFAH1B3通过降低AMPK和ACC的磷酸化水平，使脂肪酸氧化水平降低，脂质累积增加，使BRAFV600E甲状腺乳头状癌细胞对维莫非尼的耐药性增强。 |
| 关键词: BRAFV600E甲状腺乳头状癌 维莫非尼耐药性 PAFAH1B3 ACC2 脂质代谢 |
| DOI： |
| 分类号:R284.1；R917.101?????? |
| 基金项目:国家自然科学基金项目（面上项目，重点项目，重大项目） |
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| PAFAH1B3 inhibits fatty acid oxidation by down-regulating the AMPK-ACC pathway to enhance vemurafenib resistance in BRAFV600E papillary thyroid cancer cells |
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qianxuanzhen1, liling2, wuzhengyu3, huangshimei4, wangbi5, caiyan6
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1..Department of Biochemistry, School of Basic Medical Sciences, Guizhou Medical University;2.Health Quarantine Laboratory, Comprehensive Technology Center of Guiyang Customs (Guizhou International Travel Health Care Center, Port Clinic of Guiyang Customs);3.Department of Pathophysiology, School of Basic Medical Sciences, Guizhou Medical University;4.Department of forensic clinical medicine, School of forensic medicine, Guizhou Medical University;5.School of Basic Medical Sciences, Guizhou Medical University,;6.Ultrasound Center, Affiliated Hospital of Guizhou Medical University
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| Abstract: |
| ABSTRACT: OBJECTIVE To investigate whether platelet-activating factor acetylhydrolase IB3（PAFAH1B3）promotes vemurafenib resistance in BRAFV600E papillary thyroid carcinoma (PTC) cells by regulating the AMPK-ACC pathway and enhancing lipid metabolism. METHODS PCR was used to detect the mRNA expression levels of PAFAH1B3 in cells. The protein expression levels of PAFAH1B3, Bcl-2, Bax, pAMPK, AMPK, ACC2 and pACC in cells were measured using RT-PCR. Lipid accumulation in cells was assessed using Oil Red O staining, while cell apoptosis was evaluated through flow cytometry. A drug-resistant cell line was established, and the effects of PAFAH1B3 on lipid metabolism were examined through overexpression or knockdown experiments.RESULTS PAFAH1B3 expression is higher in BRAFV600E cells than BRAFwt cells (P<0.05 or P<0.001), and PAFAH1B3 expression is upregulated in BRAFV600E vemurafenib-resistant cells (P<0.0001). Upregulation of PAFAH1B3 enhances the resistance of cells to vemurafenib and reduces the apoptosis rate (P<0.05 or P<0.01). OE-PAFAH1B3 decreases AMPK phosphorylation, thereby downregulating ACC2 phosphorylation levels, which significantly reduces fatty acid oxidation levels and increases lipid accumulation in BRAFV600E cells. sh-PAFAH1B3 enhances the vemurafenib sensitivity of BRAFV600E cells, and this effect is reversed by sh-ACC2. CONCLUSION PAFAH1B3 enhances the resistance of BRAFV600E papillary thyroid cancer cells to vemurafenib by decreasing the level of fatty acid oxidation and increasing lipid accumulation through decreasing the phosphorylation levels of AMPK and ACC. |
| Key words: BRAFV600E papillary thyroid carcinoma (BRAFV600E PTC) vemurafenib resistance PAFAH1B3 ACC2 lipid metabolism |
