کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10157509 | 1666469 | 2018 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
KRAS targeting antibody synergizes anti-cancer activity of gemcitabine against pancreatic cancer
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: KRAS targeting antibody synergizes anti-cancer activity of gemcitabine against pancreatic cancer KRAS targeting antibody synergizes anti-cancer activity of gemcitabine against pancreatic cancer](/preview/png/10157509.png)
چکیده انگلیسی
Pancreatic cancer exhibits an oncogenic KRAS mutation rate of â¼90%. Despite research and drug development efforts focused on KRAS, no targeted therapy has been clinically approved for the treatment of pancreatic cancer with KRAS mutation. Also, the efficacy of gemcitabine is poor due to rapidly acquired resistance. We developed RT11-i antibody, which directly targets the intracellularly activated GTP-bound form of oncogenic RAS mutants. Here, we investigated the combined effects of RT11-i and gemcitabine in vitro and in vivo, and the mechanism involved. RT11-i significantly sensitized pancreatic cancer cells to gemcitabine. Also, the co-treatment synergistically inhibited angiogenesis, migration, and invasion, and showed synergistic anticancer activity by inhibiting the RAF/MEK/ERK or PI3K/AKT pathways. Furthermore, co-treatment inhibited endothelial barrier disruption in tumor vessels, which is a critical step in vascular leakiness of metastasis, and improved vessel structural stability. Importantly, co-treatment significantly suppressed tumor growth in an orthotopic tumor model. Taken together, our findings show that RT11-i synergistically increased the antitumor activity of gemcitabine by inhibiting RAS downstream signaling, which suggests RT11-i and gemcitabine be viewed a potential combination treatment option for pancreatic cancer patients with KRAS mutation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 438, 1 December 2018, Pages 174-186
Journal: Cancer Letters - Volume 438, 1 December 2018, Pages 174-186
نویسندگان
Yeo Wool Kang, Ji Eun Lee, Kyung Hee Jung, Mi Kwon Son, Seung-Min Shin, Soo Jung Kim, Zhenghuan Fang, Hong Hua Yan, Jung Hee Park, Boreum Han, Min Ji Cheon, Min Gyu Woo, Joo Han Lim, Yong-Sung Kim, Soon-Sun Hong,