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

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

Abstract

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.

Keywords: Akt; Drug-resistance; NEAT1; NSCLC; Shikonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Male
  • Mice
  • Naphthoquinones / administration & dosage*
  • Naphthoquinones / pharmacology
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacology
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • NEAT1 long non-coding RNA, human
  • Naphthoquinones
  • RNA, Long Noncoding
  • shikonin
  • Proto-Oncogene Proteins c-akt
  • Paclitaxel