Autor: |
Masami Suzuki, Fumiko Chiwaki, Yumi Sawada, Maho Ashikawa, Kazuhiko Aoyagi, Takeshi Fujita, Kazuyoshi Yanagihara, Masayuki Komatsu, Minoru Narita, Tsutomu Suzuki, Hiroshi Nagase, Ryoji Kushima, Hiromi Sakamoto, Takeo Fukagawa, Hitoshi Katai, Hitoshi Nakagama, Teruhiko Yoshida, Yasuhito Uezono, Hiroki Sasaki |
Jazyk: |
angličtina |
Rok vydání: |
2015 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 10, Iss 4, p e0123407 (2015) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0123407 |
Popis: |
The dormancy of tumor cells is a major problem in chemotherapy, since it limits the therapeutic efficacy of anti-tumor drugs that only target dividing cells. One potential way to overcome chemo-resistance is to "wake up" these dormant cells. Here we show that the opioid antagonist methylnaltrexone (MNTX) enhances the effect of docetaxel (Doc) by blocking a cell growth-suppressive pathway. We found that PENK, which encodes opioid growth factor (OGF) and suppresses cell growth, is predominantly expressed in diffuse-type gastric cancers (GCs). The blockade of OGF signaling by MNTX releases cells from their arrest and boosts the effect of Doc. In comparison with the use of Doc alone, the combined use of Doc and MNTX significantly prolongs survival, alleviates abdominal pain, and diminishes Doc-resistant spheroids on the peritoneal membrane in model mice. These results suggest that blockade of the pathways that suppress cell growth may enhance the effects of anti-tumor drugs. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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