白头翁皂苷 D 通过调控 ras 相关 C3 肉毒杆菌毒素底物 3（RAC3）克服肺腺癌细胞对紫杉醇的耐药性。

Pulsatilla saponin D regulates ras-related C3 botulinum toxin substrate 3 (RAC3) to overcome resistance to paclitaxel in lung adenocarcinoma cells.

机构信息

Laboratory Department of Orthopedic Spine Surgery of The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.

Key Laboratory of Surgery of Liaoning Province of The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.

出版信息

BMC Cancer. 2024 Jan 10;24(1):55. doi: 10.1186/s12885-024-11841-6.

BACKGROUND

Paclitaxel, a tubulin-binding agent, is a Food and Drug Administration-approved first-line drug for the treatment of non-small cell lung cancer (NSCLC), for both squamous and non-squamous cell lung carcinoma, with paclitaxel/carboplatin + bevacizumab a common chemotherapy regimen for stage IV non-squamous NSCLC; however, primary or acquired resistance to paclitaxel is gradually increasing, leading to treatment failure.

METHODS

Our results show that Ras-related C3 botulinum toxin substrate 3 (RAC3) is overexpressed in cultured paclitaxel-resistant cells and that RAC3 expression levels are negatively correlated with sensitivity of lung adenocarcinoma cells to paclitaxel. Pulsatilla saponin D could inhibit RAC3 expression, and we hypothesize that it may block paclitaxel resistance. Further, we found that treatment with paclitaxel combined with Pulsatilla saponin D, can overcome lung adenocarcinoma cell resistance to paclitaxel alone in cell culture and mouse xenograft models.

背景

紫杉醇是一种微管结合剂，已被美国食品药品监督管理局批准为治疗非小细胞肺癌（NSCLC）的一线药物，适用于鳞状细胞癌和非鳞状细胞癌，紫杉醇/卡铂+贝伐单抗是 IV 期非鳞状 NSCLC 的常用化疗方案；然而，紫杉醇的原发性或获得性耐药性逐渐增加，导致治疗失败。

方法

我们的结果表明，Ras 相关 C3 肉毒杆菌毒素底物 3（RAC3）在培养的紫杉醇耐药细胞中过表达，并且 RAC3 表达水平与肺腺癌细胞对紫杉醇的敏感性呈负相关。白头翁皂苷 D 可抑制 RAC3 表达，我们假设它可能阻断紫杉醇耐药性。此外，我们发现紫杉醇联合白头翁皂苷 D 治疗可在细胞培养和小鼠异种移植模型中克服肺腺癌细胞对紫杉醇的单独耐药性。