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Alantolactone sensitizes human pancreatic cancer cells to EGFR inhibitors through the inhibition of STAT3 signaling
Author(s) -
Zheng Hailun,
Yang Lehe,
Kang Yanting,
Chen Min,
Lin Shichong,
Xiang Youqun,
Li Caleb,
Dai Xuanxuan,
Huang Xiaoying,
Liang Guang,
Zhao Chengguang
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22951
Subject(s) - afatinib , stat3 , biology , pancreatic cancer , stat protein , erlotinib , cancer research , signal transduction , in vivo , egfr inhibitors , sesquiterpene lactone , erlotinib hydrochloride , epidermal growth factor receptor , cancer cell , activator (genetics) , cancer , pharmacology , receptor , microbiology and biotechnology , biochemistry , genetics , botany , sesquiterpene
Several studies have implicated the feedback activation of signal transducer and activator of transcription 3 (STAT3) as a new cancer drug‐resistance mechanism and linked it to the failure of epidermal growth factor receptor (EGFR)‐targeted therapies. In this study, we discovered that Alantolactone, a natural sesquiterpene lactone, potently inhibited human pancreatic cancer cells and suppressed constitutively activated STAT3. In contrast, Alantolactone had little effect on the EGFR pathway. Moreover, combination of Alantolactone and an EGFR inhibitor, Erlotinib or Afatinib, demonstrated a remarkable synergistic anti‐cancer effect against pancreatic cancer cells both in vitro and in vivo. Our results suggested that Alantolactone could sensitize human pancreatic cancer cells to EGFR inhibitors possibly through down‐regulating the STAT3 signaling. Alantolactone, when combined with other EGFR targeted agents, could be further developed as a potential therapy for pancreatic cancer.