Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway

Weilan Lan, Jinyan Zhao, Haixia Shang, Jun Peng, Wujin Chen, Jiumao Lin
doi: https://doi.org/10.1101/821801
Weilan Lan
1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
2Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jinyan Zhao
1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
2Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haixia Shang
1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
2Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun Peng
1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
2Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wujin Chen
3Oncology Department, Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350004, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: linjiumao@fjtcm.edu.cn chenwj8077@sina.com
Jiumao Lin
1Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
2Fujian Key Laboratory of Integrative Medicine on Geriatric, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: linjiumao@fjtcm.edu.cn chenwj8077@sina.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Background Anlotinib is a multi-tyrosine kinase inhibitor that has been reported to have activity against colorectal cancer. However, the functional mechanisms whereby anlotinib mediates against deadly drug-resistant colorectal cancer (CRC) has not been fully described-specifically, the potential mechanisms that inhibit proliferation and induce apoptosis remain largely unknown.

Methods MTT assays were used to detect cell viability and calculate the resistance index. Colony formation was used to evaluate the proliferation of resistant cells. DAPI staining was used to detect cell apoptosis morphologically. Annexin V-FITC with PI staining was used to detect early and late-stage apoptosis of cells. Cell cycle distribution was determined by Flow cytometry. Transwell assays were performed to examine the ability of migration and invasion. Cyclin D1 Survivin, CDK4, Bcl-2, Bax and changes of PI3K/AKT pathway were detected by Western blotting. Compared as a single agent or combined with anlotinib or LY294002, PI3K inhibitor (LY294002) was used to verify whether it inhibited drug-resistant CRC cells by lowering PI3K/AKT.

Results HCT-8/5-FU cells showed multiple drug resistance. Drug resistance index of 5-FU, ADM and DDP were 390.27, 2.55 and 4.57, respectively. Anlotinib was shown to inhibit cell viability on HCT-8/5-FU and HCT-8 cells for 24 h and 48 h in a dosage- and time-dependent pattern. Compared with 48 h, intervened with anlotinib (0 μM, 10 μM, 20 μM and 40 μM) for 24 h, the HCT-8/5-FU cells were sensitive to anlotinib, and their sensitivity was greater than that of the parent cell line (HCT-8) at 24 h. Further, anlotinib inhibited the number of cloned cells significantly and had a significant inhibitory effect on cell cycle, mainly by blocking G1 transferring to S phase. Moreover, anlotinib could down-regulate the expression of survivin, cyclin D1, CDK4, caspase-3, Bcl-2, MMP-2, vimentin, MMP-9, and N-cadherin, while up-regulating cleaved-caspase-3, Bax and E-cadherin. Anlotinib inhibited the activity of the PI3K/AKT pathway and induced apoptosis in HCT-8/5-FU cells. Using LY294002, a specific PI3K inhibitor, our experiment found anlotinib can inhibit drug-resistant CRC cells by reducing PI3K and p-AKT activity-induce apoptosis.

Conclusions Anlotinib inhibited the proliferation, metastasis and induced apoptosis of HCT-8 / 5-FU cells; and the mechanism could be that anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted October 28, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway
Weilan Lan, Jinyan Zhao, Haixia Shang, Jun Peng, Wujin Chen, Jiumao Lin
bioRxiv 821801; doi: https://doi.org/10.1101/821801
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway
Weilan Lan, Jinyan Zhao, Haixia Shang, Jun Peng, Wujin Chen, Jiumao Lin
bioRxiv 821801; doi: https://doi.org/10.1101/821801

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Pharmacology and Toxicology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4658)
  • Biochemistry (10311)
  • Bioengineering (7631)
  • Bioinformatics (26229)
  • Biophysics (13465)
  • Cancer Biology (10641)
  • Cell Biology (15358)
  • Clinical Trials (138)
  • Developmental Biology (8462)
  • Ecology (12774)
  • Epidemiology (2067)
  • Evolutionary Biology (16784)
  • Genetics (11370)
  • Genomics (15423)
  • Immunology (10567)
  • Microbiology (25083)
  • Molecular Biology (10170)
  • Neuroscience (54217)
  • Paleontology (398)
  • Pathology (1660)
  • Pharmacology and Toxicology (2879)
  • Physiology (4322)
  • Plant Biology (9207)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2543)
  • Systems Biology (6759)
  • Zoology (1456)