FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4214891614> ?p ?o ?g. }

• W4214891614 endingPage "601" @default.
• W4214891614 startingPage "601" @default.
• W4214891614 abstract "The microtubule-targeting agents (MTAs) are well-known chemotherapeutic agents commonly used for therapy of a broad spectrum of human malignancies, exhibiting epithelial origin, including breast, lung, and prostate cancer. Despite the impressive response rates shortly after initiation of MTA-based therapy, the vast majority of human malignancies develop resistance to MTAs due to the different mechanisms. Here, we report that infigratinib (BGJ 398), a potent FGFR1-4 inhibitor, restores sensitivity of a broad spectrum of ABCB1-overexpressing cancer cells to certain chemotherapeutic agents, including paclitaxel (PTX) and doxorubicin (Dox). This was evidenced for the triple-negative breast cancer (TNBC), and gastrointestinal stromal tumor (GIST) cell lines, as well. Indeed, when MDR-overexpressing cancer cells were treated with a combination of BGJ 398 and PTX (or Dox), we observed a significant increase of apoptosis which was evidenced by an increased expression of cleaved forms of PARP, caspase-3, and increased numbers of Annexin V-positive cells, as well. Moreover, BGJ 398 used in combination with PTX significantly decreased the viability and proliferation of the resistant cancer cells. As expected, no apoptosis was found in ABCB1-overexpressing cancer cells treated with PTX, Dox, or BGJ 398 alone. Inhibition of FGFR-signaling by BGJ 398 was evidenced by the decreased expression of phosphorylated (i.e., activated) forms of FGFR and FRS-2, a well-known adaptor protein of FGFR signaling, and downstream signaling molecules (e.g., STAT-1, -3, and S6). In contrast, expression of MDR-related ABC-transporters did not change after BGJ 398 treatment, thereby suggesting an impaired function of MDR-related ABC-transporters. By using the fluorescent-labeled chemotherapeutic agent PTX-Alexa488 (Flutax-2) and doxorubicin, exhibiting an intrinsic fluorescence, we found that BGJ 398 substantially impairs their efflux from MDR-overexpressing TNBC cells. Moreover, the efflux of Calcein AM, a well-known substrate for ABCB1, was also significantly impaired in BGJ 398-treated cancer cells, thereby suggesting the ABCB1 as a novel molecular target for BGJ 398. Of note, PD 173074, a potent FGFR1 and VEGFR2 inhibitor failed to retain chemotherapeutic agents inside ABCB1-overexpressing cells. This was consistent with the inability of PD 173074 to sensitize Tx-R cancer cells to PTX and Dox. Collectively, we show here for the first time that BGJ 398 reverses the sensitivity of MDR-overexpressing cancer cells to certain chemotherapeutic agents due to inhibition of their efflux from cancer cells via ABCB1-mediated mechanism." @default.
• W4214891614 created "2022-03-05" @default.
• W4214891614 creator A5005103392 @default.
• W4214891614 creator A5009382841 @default.
• W4214891614 creator A5012382655 @default.
• W4214891614 creator A5037302507 @default.
• W4214891614 creator A5051188246 @default.
• W4214891614 creator A5062609714 @default.
• W4214891614 creator A5066600298 @default.
• W4214891614 creator A5071534404 @default.
• W4214891614 date "2022-03-03" @default.
• W4214891614 modified "2023-10-17" @default.
• W4214891614 title "Infigratinib (BGJ 398), a Pan-FGFR Inhibitor, Targets P-Glycoprotein and Increases Chemotherapeutic-Induced Mortality of Multidrug-Resistant Tumor Cells" @default.
• W4214891614 cites W113485429 @default.
• W4214891614 cites W124504601 @default.
• W4214891614 cites W1533444088 @default.
• W4214891614 cites W1546346721 @default.
• W4214891614 cites W1574460503 @default.
• W4214891614 cites W1577206371 @default.
• W4214891614 cites W1696775091 @default.
• W4214891614 cites W1780912673 @default.
• W4214891614 cites W1791352086 @default.
• W4214891614 cites W1874417368 @default.
• W4214891614 cites W1964709116 @default.
• W4214891614 cites W1965816291 @default.
• W4214891614 cites W1970174659 @default.
• W4214891614 cites W1970218983 @default.
• W4214891614 cites W1972960351 @default.
• W4214891614 cites W1975691556 @default.
• W4214891614 cites W1981376295 @default.
• W4214891614 cites W1984246155 @default.
• W4214891614 cites W1993043513 @default.
• W4214891614 cites W1995864713 @default.
• W4214891614 cites W1997730952 @default.
• W4214891614 cites W1997878542 @default.
• W4214891614 cites W2002038028 @default.
• W4214891614 cites W2003640047 @default.
• W4214891614 cites W2006583554 @default.
• W4214891614 cites W2011906439 @default.
• W4214891614 cites W2015996393 @default.
• W4214891614 cites W2016318120 @default.
• W4214891614 cites W2019346113 @default.
• W4214891614 cites W2020946741 @default.
• W4214891614 cites W2025950197 @default.
• W4214891614 cites W2032167680 @default.
• W4214891614 cites W2038695289 @default.
• W4214891614 cites W2047282772 @default.
• W4214891614 cites W2051776823 @default.
• W4214891614 cites W2052362392 @default.
• W4214891614 cites W2055904567 @default.
• W4214891614 cites W2056163905 @default.
• W4214891614 cites W2067596492 @default.
• W4214891614 cites W2067815150 @default.
• W4214891614 cites W2068092421 @default.
• W4214891614 cites W2069907205 @default.
• W4214891614 cites W2070791205 @default.
• W4214891614 cites W2075093463 @default.
• W4214891614 cites W2076174476 @default.
• W4214891614 cites W2081182696 @default.
• W4214891614 cites W2081538957 @default.
• W4214891614 cites W2091371557 @default.
• W4214891614 cites W2093197708 @default.
• W4214891614 cites W2095646155 @default.
• W4214891614 cites W2098064809 @default.
• W4214891614 cites W2098712825 @default.
• W4214891614 cites W2098785293 @default.
• W4214891614 cites W2103177188 @default.
• W4214891614 cites W2103796073 @default.
• W4214891614 cites W2105968397 @default.
• W4214891614 cites W2106742754 @default.
• W4214891614 cites W2107277218 @default.
• W4214891614 cites W2108934318 @default.
• W4214891614 cites W2117122875 @default.
• W4214891614 cites W2118443127 @default.
• W4214891614 cites W2119010359 @default.
• W4214891614 cites W2120635383 @default.
• W4214891614 cites W2124992781 @default.
• W4214891614 cites W2125695832 @default.
• W4214891614 cites W2129342281 @default.
• W4214891614 cites W2131058993 @default.
• W4214891614 cites W2138851039 @default.
• W4214891614 cites W2139910235 @default.
• W4214891614 cites W2140247386 @default.
• W4214891614 cites W2146440927 @default.
• W4214891614 cites W2150322923 @default.
• W4214891614 cites W2155383511 @default.
• W4214891614 cites W2157923000 @default.
• W4214891614 cites W2159587676 @default.
• W4214891614 cites W2161000665 @default.
• W4214891614 cites W2163186938 @default.
• W4214891614 cites W2167036588 @default.
• W4214891614 cites W2169302611 @default.
• W4214891614 cites W2171223909 @default.
• W4214891614 cites W2192080449 @default.
• W4214891614 cites W2245825568 @default.
• W4214891614 cites W2253853328 @default.
• W4214891614 cites W2500192509 @default.
• W4214891614 cites W2556113557 @default.

• next