Abstract 98: Stromal-targeting with quercetin in patient-derived models of head and neck squamous cell carcinoma (HNSCC)

头颈部鳞状细胞癌 槲皮素 顺铂 间质细胞 癌症研究 医学 癌症 体内 类黄酮 癌细胞 头颈部癌 药理学 肿瘤科 内科学 化疗 化学 生物 生物化学 生物技术 抗氧化剂
作者
Hui Li,Wenying Piao,Pik Yuk Lau,Chin Wang Lau,Jason Y. K. Chan,Yu‐Xiong Su,Leaf Huang,Kai Hu,Vivian Wai Yan Lui
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:79 (13_Supplement): 98-98 被引量:1
标识
DOI:10.1158/1538-7445.am2019-98
摘要

Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with a high recurrence rate. Recurrences occur in ~25% cases of early -stage patients (Stage I-II) and 50-60% cases of advanced stage (Stage II-IV) patients. Cumulative evidences suggest that tumor stroma, especially cancer-associated fibroblast (CAF) plays a protective role and contributes to drug-resistance in HNSCC, leading to recurrences after treatment. Quercetin is a flavonoid purified from natural plants, such as green tea, onions and berries. It has been reported to suppress CAFs and reduce collagen accumulation surrounding tumors, potentially facilitating drug delivery to tumors. Here, we hypothesize that quercetin targeting of CAFs may enhance the anti-tumor efficacy of cisplatin, and potentially other antitumor therapies in HNSCC. Using a primary co-culture system with primary HNSCC cells (70%) and the paired CAFs (30%) from HNSCC patients, we investigated the effect of quercetin and cisplatin combination treatment in vitro. We found that combination of quercetin and cisplatin elicited a significantly greater growth inhibition (70% of inhibition) as compared to 37% of inhibition with cisplatin and 15% of inhibition with quercetin alone. This result appeared to demonstrate some anti-CAF effects and antitumor effects exerted by this combination strategy.Using patient-derived HNSCC primary tumor cells, stromal-rich xenografts were successfully developed in vivo. The stromal-suppressive effect of quercetin was then examined upon treatment with increasing doses of quercetin (DMF, 2.5, 5 or 10 μM in 5 microliter volume, 2 times injection). Potential alteration of the tumor architecture by quercetin (vs. vehicle treatment) was examined by H&E staining. A marked reduction of stromal component was found in quercetin -treated tumors vs. vehicle-treated tumors. Importantly, we also found that these quercetin-treated tumors have 80.4% reduction in α-SMA protein expression (6.0% in vehicle vs.1.2% in treatment group), strongly indicating a significant stromal suppressive action of quercetin in an HNSCC primary culture-derived xenograft model. Furthermore, quercetin (10 μM) treatment reduced collagen expression by ~80% (vs. vehicle treatment) in the HNSCC primary culture-derived xenograft model by Masson’s trichrome staining. In conclusion, quercetin can effectively suppress the activated status of CAFs and may potentially enhance anti-tumor effect of cisplatin in an HNSCC patient-relevant manner. The antitumor efficacy of quercetin combination strategies should warrant further investigations. Citation Format: Hui Li, Wenying Piao, Pik Yuk Lau, Chin Wang Lau, Jason Ying Kuen Chan, Yu Xiong Su, Leaf Huang, Kai Li Hu, Vivian Wai Yan Lui. Stromal-targeting with quercetin in patient-derived models of head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 98.

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
科研通AI2S应助swordlee采纳,获得10
1秒前
1秒前
lng98发布了新的文献求助10
1秒前
赘婿应助树影采纳,获得10
1秒前
自由念之完成签到,获得积分10
2秒前
慕子默完成签到,获得积分10
2秒前
一八四发布了新的文献求助10
2秒前
月下发布了新的文献求助10
3秒前
3秒前
yang发布了新的文献求助10
4秒前
elva发布了新的文献求助20
4秒前
bkagyin应助哒哒哒采纳,获得10
4秒前
4秒前
5秒前
赤墨完成签到,获得积分10
5秒前
哇哇哇哇发布了新的文献求助10
6秒前
Elmore发布了新的文献求助10
6秒前
6秒前
自觉的道罡完成签到,获得积分10
6秒前
科目三应助陈伟杰采纳,获得10
6秒前
奇怪的柒完成签到,获得积分10
7秒前
感冒了完成签到,获得积分10
7秒前
怕黑念薇完成签到,获得积分10
7秒前
8秒前
8秒前
8秒前
燕尾蝶F完成签到,获得积分10
8秒前
所所应助lihua采纳,获得10
9秒前
故意的可愁完成签到 ,获得积分10
9秒前
义气如萱完成签到 ,获得积分10
9秒前
haozi王完成签到,获得积分10
9秒前
10秒前
10秒前
10秒前
10秒前
11秒前
11秒前
小蘑菇应助Sunny采纳,获得10
11秒前
小米稀饭完成签到 ,获得积分10
12秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Mechanistic Modeling of Gas-Liquid Two-Phase Flow in Pipes 2500
Kelsen’s Legacy: Legal Normativity, International Law and Democracy 1000
Handbook on Inequality and Social Capital 800
Conference Record, IAS Annual Meeting 1977 610
Interest Rate Modeling. Volume 3: Products and Risk Management 600
Interest Rate Modeling. Volume 2: Term Structure Models 600
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3546536
求助须知:如何正确求助?哪些是违规求助? 3123667
关于积分的说明 9356348
捐赠科研通 2822331
什么是DOI,文献DOI怎么找? 1551314
邀请新用户注册赠送积分活动 723326
科研通“疑难数据库(出版商)”最低求助积分说明 713699