Regulatory mechanisms of PESV in reversing imatinib resistance in chronic myeloid leukemia at the molecular level

ZHANG weifeng; WANG Xingli; YANG Xiangdong; YANG Wenhua; HAO Zheng; ZENG Lirong; ZHANG Ying

doi:10.16025/j.1674-1307.2026.03.014

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Regulatory mechanisms of PESV in reversing imatinib resistance in chronic myeloid leukemia at the molecular level

更新时间：2026-06-02

- Regulatory mechanisms of PESV in reversing imatinib resistance in chronic myeloid leukemia at the molecular level
- Beijing Journal of Traditional Chinese Medicine Vol. 45, Issue 3, Pages: 366-372(2026)
- 作者机构：
  
  1.天津中医药大学第一附属医院中医国家针灸临床医学研究中心，天津 300381
  2.天津中医药大学，天津 301617
- 作者简介：
- 基金信息：
- DOI：10.16025/j.1674-1307.2026.03.014
  CLC：
- Received：25 April 2025，
  
  Published：25 March 2026
- 稿件说明：
移动端阅览
张伟锋，王兴丽，杨向东，等.蝎毒多肽逆转慢性粒细胞白血病伊马替尼耐药的分子调节机制研究［J］.北京中医药，2026，45（3）：366-372.

ZHANG weifeng,WANG Xingli,YANG Xiangdong,et al.Regulatory mechanisms of PESV in reversing imatinib resistance in chronic myeloid leukemia at the molecular level[J]. Beijing Journal of Traditional Chinese Medicine,2026,45(03):366-372.
张伟锋，王兴丽，杨向东，等.蝎毒多肽逆转慢性粒细胞白血病伊马替尼耐药的分子调节机制研究［J］.北京中医药，2026，45（3）：366-372. DOI： 10.16025/j.1674-1307.2026.03.014.

ZHANG weifeng,WANG Xingli,YANG Xiangdong,et al.Regulatory mechanisms of PESV in reversing imatinib resistance in chronic myeloid leukemia at the molecular level[J]. Beijing Journal of Traditional Chinese Medicine,2026,45(03):366-372. DOI： 10.16025/j.1674-1307.2026.03.014.

摘要

目的

观察蝎毒多肽提取物（PESV）对慢性粒细胞白血病（CML）伊马替尼（IM）耐药K562/R细胞Hedgehog（HH）信号通路上游活化因子的影响，探讨其分子调节机制。

方法

建立IM耐药细胞株K562/R，应用CCK-8法检测PESV对K562/R细胞增殖抑制率，应用流式细胞术检测细胞凋亡率，用PCR、Western blot法检测PESV低、中、高剂量组、IM组、PESV+IM组及对照组细胞上游活化因子Shh、Smo、Ptch mRNA及其蛋白表达。取BALB/c荷瘤鼠，分为PESV低、中、高剂量组、IM组、PESV+IM组、对照组并按设定方法给药，观察小鼠生存状态、体质量变化，计算各治疗组的抑瘤率，取瘤组织提取单个核细胞悬液，应用RT-PCR、Western blot检测各组小鼠瘤组织细胞上游活化因子Shh、Smo、Ptch mRNA及蛋白的表达。

结果

与对照组比较，各组对IM耐药细胞株K562/R细胞的BCR/ABL融合基因mRNA表达和P210

bcr/abl

蛋白表达均有不同程度的抑制作用，其中以PESV+IM组效果最为明显（

0.05）；PESV中剂量组与IM组表达水平相当（

0.05），PESV低、高剂量组表达均高于IM组（

0.05），而PESV+IM组的表达明显低于IM组（

0.05）。与对照组比较，各组小鼠瘤组织细胞Shh、Smo、Ptch基因mRNA和蛋白表达均下降（

0.05）；PESV中剂量组Shh、Smo、Ptch基因mRNA和蛋白表达均低于低、高剂量组（

0.05），而与IM组差异无统计学意义（

0.05），PESV+IM组3个基因mRNA和蛋白表达均低于其他各组（

0.05）。

结论

PESV能够通过抑制上游HH配体蛋白的表达及活化，从而抑制K562/R细胞的增殖并促进其凋亡，以此逆转IM耐药。

Abstract

Objective

To observe the effects of Polypeptide Extract from Scorpion Venom（PESV） extract on upstream activators of the Hedgehog （Hh） signaling pathway in imatinib （IM）-resistant chronic myeloid leukemia （CML） K562/R cells and to explore its molecular regulatory mechanisms.

Methods

An IM-resistant K562/R cell line was established. The CCK-8 assay was used to determine the proliferation inhibition rate of PESV on K562/R cells， and flow cytometry was used to assess apoptosis. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of upstream activators Shh， Smo， and Ptch in each group. BALB/c tumor-bearing mice were established and treated according to the experimental protocol. Survival status and body weight changes were observed， and tumor inhibition rates were calculated. Tumor tissues were collected to prepare single-cell suspensions， and RT-PCR and Western blot were used to detect the mRNA and protein expression levels of Shh， Smo， and Ptch in tumor tissues.

Results

Compared with the control group， all treatment groups showed varying degrees of inhibition of BCR/ABL fusion gene mRNA expression and P210 BCR/ABL protein expression in K562/R cells， with the PESV + IM group showing the most significant effect （

0.05）. The medium-dose PESV group showed expression levels comparable to the IM group （

0.05）， while the low- and high-dose PESV groups showed higher expression levels than the IM group （

0.05）. The expression levels in the PESV + IM group were significantly lower than those in the IM group （

0.05）. Compared with the control group， the mRNA and protein expression levels of Shh， Smo， and Ptch in tumor tissues were significantly reduced in all groups （

0.05）. In the PESV medium-dose group， the expression levels of all three genes at both mRNA and protein levels were lower than those in the low- and high-dose groups （

0.05）， with no statistically significant difference compared with the IM group （

0.05）. The PESV + IM group showed the lowest expression levels of all three genes among all groups （

0.05）.

Conclusion

PESV can inhibit proliferation and promote apoptosis of K562/R cells by suppressing the expression and activation of upstream Hedgehog pathway ligands， thereby reversing IM resistance.

关键词

Keywords

references

宋艳芳 , 罗丽 , 施鹏冲 , 等 . Cyr61对慢性粒细胞白血病伊马替尼耐药的影响及其机制研究 [J ] . 中国实验血液学杂志 , 2023 , 31 ( 1 ): 1 - 7 .

BRAUN TP , EIDE CA , DRUKER BJ . Response and Resistance to BCR-ABL1-Targeted Therapies [J ] . Cancer Cell , 2020 , 37 ( 4 ): 530 - 542 .

AZIZIDOOST S , NASROLAHI A , SHEYKHI-SABZEHPOUSH M , et al . Signaling pathways governing the behaviors of leukemia stem cells [J ] . Genes Dis , 2023 , 11 ( 2 ): 830 - 846 .

杜阳帆 , 闫理想 , 郭江水 , 等 . 史哲新教授治疗老年急性髓系白血病用药规律探析：基于数据挖掘技术 [J ] . 亚太传统医药 , 2023 , 19 ( 11 ): 215 - 220 .

杨向东 , 王兴丽 , 杨文华 , 等 . 蝎毒多肽逆转白血病干细胞多药耐药作用的研究 [J ] . 中国中药杂志 , 2016 , 41 ( 24 ): 4648 - 4653 .

郝征 , 杨文华 . 蝎毒多肽干预急性白血病髓外浸润传变的机制 [J ] . 中华中医药杂志 , 2012 , 27 ( 04 ): 1106 - 1110 .

张伟锋 , 杨文华 . 蝎毒多肽对慢性粒细胞白血病细胞Hh通路下游活化因子Gli1表达的影响 [J ] . 山东医药 , 2018 , 58 ( 20 ): 25 - 27 .

蓝海 , 侯丽 , 郎海燕 , 等 . 常见血液病的中医分类与命名 [J ] . 中医杂志 , 2019 , 60 ( 09 ): 750 - 753,778 .

韩保升 . 蜀本草 [M ] . 合肥：安徽科学技术出版社， 2005 : 211 .

陈玥灿 , 陈信义 , 郎海燕 . 陈信义基于“浊毒病机论”分期辨治恶性淋巴瘤经验撷要 [J ] . 北京中医药 , 2024 , 43 ( 10 ): 1088 - 1091 .

宁淑博 , 邵新 , 冉志芳 , 等 . 蝎毒多肽药用价值研究现状 [J ] . 山东中医杂志 , 2024 , 43 ( 11 ): 1301 - 1308 .

杨向东 , 史哲新 , 闫理想 , 等 . 从白血病干细胞水平研究蝎毒多肽提取物逆转多药耐药机制 [J ] . 中国中西医结合杂志 , 2016 , 36 ( 7 ): 867 - 874 .

GDESZ-BIRULA K , DROBCZYŃSKI S , SARAT K , et al . Sonidegib inhibits the adhesion of acute myeloid leukemia to the bone marrow in hypoxia: an optical tweezer study [J ] . Biomedicines , 2025 , 13 ( 3 ): 578 .

SICURELLA M , DE CHIARA M , NERI LM . Hedgehog and PI3K/Akt/mTOR signaling pathways involvement in leukemic malignancies: crosstalk and role in cell death [J ] . Cells , 2025 , 14 ( 4 ): 269 .

ZHUANG R , SIEBELS B , HOFFER K , et al . Functional role of fatty acid synthase for signal transduction in core-binding factor acute myeloid leukemia with an activating c-Kit mutation [J ] . Biomedicines , 2025 , 13 ( 3 ): 619 .

杨茜茹 , 田劭丹 , 薛程元 , 等 . 复方浙贝颗粒基于MDM2/p53信号通路调节MHC-Ⅱ逆转白血病多药耐药机制研究 [J ] . 北京中医药 , 2025 , 44 ( 3 ): 325 - 330 .

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