探讨传统中药单体衍生物血竭素高氯酸盐（DP）逆转结直肠癌奥沙利铂（L-OHP）获得性耐药的增敏效应，并阐明其基于PI3K/Akt信号通路及抗凋亡网络的潜在分子机制。

采用逐步浓度递增法诱导建立人结直肠癌L-OHP耐药细胞株（SW480/L-OHP）。通过CCK-8法与CompuSyn软件评估低毒剂量DP联合L-OHP的协同增敏效应，并利用平板克隆形成实验评估其对细胞长效增殖潜能的影响；采用Annexin V-FITC/PI双染流式细胞术检测细胞凋亡水平；通过蛋白印迹法（western blot）检测PI3K/Akt信号通路靶点，以及下游凋亡相关蛋白的表达变化。采用GraphPad Prism 9.0软件进行统计分析，符合正态分布的定量数据以 (

成功构建具有上皮-间质转化（EMT）特征及抗凋亡表型的耐药株SW480/L-OHP；CCK-8与克隆形成实验表明，10 μmol/L低毒性剂量的DP与L-OHP联用表现出显著的协同作用（CI < 1），耐药细胞对L-OHP的半数抑制浓度（IC50）由单药时的40.9 μmol/L下降至3.8 μmol/L，逆转倍数达10.7，且有效抑制了克隆形成能力（P<0.000 1）；流式细胞术表明，联合用药克服了耐药细胞的凋亡抵抗，细胞总凋亡率升高至21.1%（P<0.000 1）；机制分析表明，联合用药有效抑制了耐药细胞中PI3K和Akt的磷酸化水平，从而下调抗凋亡蛋白Bcl-2，上调促凋亡蛋白Bax的表达，重塑了耐药细胞的凋亡蛋白稳态。

血竭素高氯酸盐是一种具有临床转化前景的奥沙利铂化疗增敏剂。其可通过协同靶向阻断PI3K/Akt信号通路，重塑抗凋亡网络，从而有效逆转结直肠癌细胞获得性耐药表型，为克服临床化疗耐药提供了新的中西医结合治疗策略。

To investigate the sensitizing effect of the high-chloride salt of the traditional Chinese medicine monomer derivative, dihydroperiplanarol (DP), in reversing the acquired resistance of colorectal cancer to oxaliplatin (L-OHP), and to elucidate its potential molecular mechanism based on the PI3K/Akt signaling pathway and the anti-apoptotic network.

The human colorectal cancer L-OHP-resistant cell line (SW480/L-OHP) was established by a stepwise concentration increment method. The synergistic sensitizing effect of low-toxicity DP combined with L-OHP was evaluated by the CCK-8 method and CompuSyn software, and the effect on the long-term proliferation potential of the cells was assessed by the plate colony formation experiment. The apoptosis level was detected by Annexin V-FITC/PI double staining flow cytometry. The expression changes of PI3K/Akt signaling pathway targets and downstream apoptosis-related proteins were detected by Western blot. Statistical analysis was performed using GraphPad Prism 9.0 software. Quantitative data were expressed as (

The resistant cell line SW480/L-OHP with epithelial-mesenchymal transition (EMT) characteristics and anti-apoptotic phenotype was successfully constructed. The CCK-8 and colony formation experiments showed that the combination of 10 μmol/L low-toxicity DP and L-OHP exhibited significant synergy (CI<1), and the half inhibitory concentration (IC50) of L-OHP for the resistant cells decreased from 40.9 μmol/L to 3.8 μmol/L, with a reversal ratio of 10.7, and effectively inhibited the colony formation ability (P<0.000 1). Flow cytometry indicated that the combination treatment overcame the apoptosis resistance of the resistant cells, and the total apoptosis rate increased to 21.1% (P<0.000 1). Mechanism analysis showed that the combination treatment effectively inhibited the phosphorylation levels of PI3K and Akt in the resistant cells, thereby down-regulating the anti-apoptotic protein Bcl-2 and up-regulating the expression of pro-apoptotic protein Bax, and reshaping the apoptosis protein homeostasis of the resistant cells.

Dihydroperiplanarol high-chloride salt is a clinically promising chemotherapy sensitizing agent for oxaliplatin. It can effectively reverse the acquired resistance phenotype of colorectal cancer cells by synergistically targeting and blocking the PI3K/Akt signaling pathway and reshaping the anti-apoptotic network, providing a new combined traditional Chinese and Western medicine treatment strategy to overcome clinical chemotherapy resistance.