Targeting COX-2 potently inhibits proliferation of cancer cells in vivo but not in vitro in cutaneous squamous cell carcinoma.
Targeting COX-2 potently inhibits proliferation of cancer cells in vivo but not in vitro in cutaneous squamous cell carcinoma.
复制标题
靶向 COX-2 可在体内有效抑制皮肤鳞状细胞癌癌细胞的增殖，但在体外则无效
DOI：
10.21037/tcr-20-3527
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发表时间：
2021-05
影响因子：
0.9
通讯作者：
Liao XH
中科院分区：
文献类型：
--
作者：
Gao L;Wang TH;Chen CP;Xiang JJ;Zhao XB;Gui RY;Liao XH
研究背景环氧合酶2（考克斯-2）是一种诱导型酶，在多种癌症中促进肿瘤发生。考克斯-2基因敲除可显著抑制皮肤鳞状细胞癌（SCC）的发生。然而，在以往的报道中，考克斯-2抑制剂治疗对SCC仅表现出轻度至中度的抑制。本研究旨在解决这一矛盾，并重新评估靶向考克斯-2在SCC中的治疗潜力。方法采用shRNA技术，在A431和SCC-13两种不同的SCC细胞系中，敲低考克斯-2。采用细胞生长曲线和单层划痕实验检测细胞的增殖能力和迁移能力。还将具有考克斯-2敲低的癌细胞异种移植到Balb/c裸鼠中，并记录随时间的肿瘤生长曲线。此外，我们改变给药途径，腹腔注射考克斯-2抑制剂塞来昔布到小鼠体内，以评估其抗癌活性。结果在体外，考克斯-2基因的敲除对两种不同的SCC细胞系的增殖和迁移能力均无影响。然而，当将癌细胞异种移植到裸鼠中时，考克斯-2的敲低显著抑制了肿瘤中癌细胞的增殖。最后，腹腔注射而不是口服考克斯-2抑制剂塞来昔布有效地抑制肿瘤生长。结论考克斯-2可能通过影响癌细胞与周围微环境的相互作用而非直接作用于癌细胞，提示以考克斯-2为靶点治疗SCC是一种非常有前景的治疗方法。
Background Cyclooxygenase 2 (COX-2) is an inducible enzyme which promotes tumorigenesis in many types of cancers. Genetic knockout of COX-2 significantly suppresses the tumorigenesis of skin squamous cell carcinoma (SCC). However, COX-2 inhibitor treatment only showed mild to moderate inhibition on SCC in previous reports. The aim of this study is to solve this contradiction and to re-evaluate the therapeutic potential of targeting COX-2 in SCC. Methods COX-2 was knocked down by shRNA in two different SCC cell lines, A431 and SCC-13. The cells proliferation and migration capacity were evaluated by cell growth curves and monolayer scratch assay, respectively. Cancer cells with COX-2 knockdown were also xenografted into Balb/c nude mice and tumor growth curves were recorded over time. In addition, we changed the drug administration route and intraperitoneally injected COX-2 inhibitor celecoxib into mice to evaluate its anti-cancer activity. Results Knockdown of COX-2 exhibited mild or even no effect on cell proliferation and migration in two different SCC cell lines in vitro. However, when cancer cells were xenografted into nude mice, knockdown of COX-2 significantly suppressed proliferation of cancer cells in tumors. At last, intraperitoneal injection instead of oral administration of COX-2 inhibitor celecoxib potently suppressed tumor growth. Conclusions Our results indicate that COX-2 might impact on the interaction between cancer cells and surrounding microenvironments rather than on cancer cells directly, and demonstrate that targeting COX-2 is a very promising therapeutic approach for SCC treatment.