紫草素通过抑制 NEAT1 和 Akt 信号通路治疗紫杉醇耐药的非小细胞肺癌。

Shikonin suppresses NEAT1 and Akt signaling in treating paclitaxel-resistant non-small cell of lung cancer.

机构信息

Department of Respiratory and Oncology, Changxing County People's Hospital, Changxing, Zhejiang, 313100, People's Republic of China.

Department of Oncology, Zhejiang Hospital, No.12 Lingyin Road, Hangzhou, Zhejiang, 310013, People's Republic of China.

出版信息

Mol Med. 2020 Apr 8;26(1):28. doi: 10.1186/s10020-020-00152-8.

BACKGROUND

The development of paclitaxel-resistance led to the tumor relapse and treatment failure of non-small cell lung cancer. Shikonin has been demonstrated to show anti-cancer activity in many cancer types. The present study aimed to investigate the anti-cancer activity of shikonin in paclitaxel-resistant non-small cell lung cancer treatment.

METHODS

MTT, clonogenic assay, apoptotic cell death analysis, western blot, qRT-PCR, gene knockdown and overexpression, xenograft experiment, immunohistochemistry were performed.

RESULTS

Shikonin decreased paclitaxel-resistant NSCLC cell viability and inhibited the growth of xenograft tumor. Shikonin induced apoptotic cell death of paclitaxel-resistant NSCLC cell lines and suppressed the level of NEAT1 and Akt signaling of paclitaxel-resistant NSCLC cell lines and xenograft tumors. Either low dose or high dose of shikonin considerably suppressed the cell growth and induced the cell apoptotic death in NEAT1 knockdown A549/PTX cells, and p-Akt expression was decreased.

CONCLUSIONS

Shikonin could be a promising candidate for paclitaxel-resistant NSCLC treatment.

背景

紫杉醇耐药的发展导致非小细胞肺癌的肿瘤复发和治疗失败。紫草素已被证明在多种癌症类型中具有抗癌活性。本研究旨在探讨紫草素在紫杉醇耐药非小细胞肺癌治疗中的抗癌活性。

方法

采用 MTT、集落形成实验、凋亡细胞死亡分析、Western blot、qRT-PCR、基因敲低和过表达、异种移植实验、免疫组化等方法进行研究。

结果

紫草素降低紫杉醇耐药非小细胞肺癌细胞活力，抑制异种移植肿瘤生长。紫草素诱导紫杉醇耐药非小细胞肺癌细胞系的凋亡细胞死亡，并抑制紫杉醇耐药非小细胞肺癌细胞系和异种移植肿瘤中 NEAT1 和 Akt 信号通路的水平。低剂量或高剂量的紫草素均可显著抑制 NEAT1 敲低的 A549/PTX 细胞的细胞生长，并诱导细胞凋亡死亡，同时降低 p-Akt 的表达。