GSTDTAP  > 气候变化
Oncotarget: The drug sensitivity of hepatocellular cancer cells
admin
2021-06-07
发布年2021
语种英语
国家美国
领域气候变化 ; 地球科学 ; 资源环境
正文(英文)
IMAGE

IMAGE: Drug sensitivity of cells cultured in standard and native conditions. The IC50 values of respective drugs (x-axis) of respective cells (respective charts) cultured in native (white bars) and standard (black... view more 

Credit: Correspondence to - Richie Soong - mdcrcts@nus.edu.sg and Bhaskar Bhattacharya - bhaskar@pascific.com

Oncotarget published "Effect of cell microenvironment on the drug sensitivity of hepatocellular cancer cells" which reported that this study aimed to investigate whether Hepatocellular Cancer (HCC) cells cultured in more native conditions have an altered phenotype and drug sensitivity compared to those cultured in standard conditions.

Six HCC cell lines were cultured in "standard" or more "native" conditions.

HCC cells cultured in native conditions had slower doubling times, increased HK2 and GLUT, lower PHDA and ATP levels, and mutations in mitochondrial DNA.

From 90 comparisons of drug sensitivity, increased resistance and sensitivity for cells cultured in native conditions was observed in 14 and 8 comparisons respectively.

Therefore, cells cultured in more native conditions can have a more glycolytic and aggressive phenotype and varied drug sensitivity to those cultured in standard conditions, and may provide new insights to understanding tumor biology and drug development.

Dr. Richie Soong and Dr. Bhaskar Bhattacharya said, "Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide, with a poor median survival time after diagnosis of six months."

"Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide, with a poor median survival time after diagnosis of six months."

Lactate is also high in the HCC microenvironment, owing to the Warburg effect under which tumor cells convert glucose into lactate with an overall less production of Adenosine triphosphate (ATP) compared to mitochondrial oxidative phosphorylation.

As understanding of the tumor microenvironment has increased over time, it has become apparent that the historical culture conditions do not reflect the native tumor microenvironment well, including having increased glucose, increased oxygen, and reduced lactic acid concentrations.

The Oncotarget authors previously showed that gastric cancer cells cultured in low glucose compared to standard high glucose levels had an increased resistance to 5-fluorouracil and carboplatin - concomitant with increased glycolysis and mitochondrial mutation.

This led us to postulate that culturing cells in glucose, oxygen, and lactate conditions that are more consistent with the native tumor microenvironment may provide a better assessment of drug sensitivity, and help lead to higher success rates in drug development.

The goal of this Oncotarget study was to characterize the effect of culturing HCC cells in native compared to standard culture conditions on cellular and molecular phenotypes and drug sensitivity.

The Soong/Bhattacharya Research Team concluded in their Oncotarget Research Output, "we cultured HCC cells in its native environment compared to standard culture conditions, and observed phenotypic and molecular signatures of cells in native conditions pathologically similar to human HCC. The study highlights two important points,

A.New insights in pathogenesis could be gained by culturing cells in conditions closer to physiological conditions, and

B.A better idea of therapeutic response may be obtained by screening experimental agents in cancer cells grown in a microenvironment similar to actual disease setting.

Culturing cells in their native conditions has the potential to identify therapy, either single agent or combination, which would have otherwise been considered ineffective under the currently used artificial environment. Additionally, novel targets may also be identified under native conditions in addition to refining our existing knowledge of tumor biology. Nonetheless, it is important to keep in perspective the exhaustive work of manually concurrently culturing cells in standard and native conditions, and conducting the diverse interrogations, limited this study to understanding of a few cell lines, mechanisms and drugs. Future studies incorporating high-throughput culturing and screening methods, and the testing of other hypotheses and timepoints will help to reveal the scope of generalizability of these findings."

###

DOI - https://doi.org/10.18632/oncotarget.27910

Full text - https://www.oncotarget.com/article/27910/text/

Correspondence to - Richie Soong - mdcrcts@nus.edu.sg and Bhaskar Bhattacharya - bhaskar@pascific.com

Keywords - drug development, microenvironment, glycolysis

About Oncotarget

Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957x105

Copyright © 2021 Impact Journals, LLC
Impact Journals is a registered trademark of Impact Journals, LLC

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

URL查看原文
来源平台EurekAlert
文献类型新闻
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/329136
专题气候变化
地球科学
资源环境科学
推荐引用方式
GB/T 7714
admin. Oncotarget: The drug sensitivity of hepatocellular cancer cells. 2021.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[admin]的文章
百度学术
百度学术中相似的文章
[admin]的文章
必应学术
必应学术中相似的文章
[admin]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。