Alantolactone sensitizes human pancreatic cancer cells to EGFR inhibitors through the inhibition of STAT3 signaling

被引：52

作者：

Zheng, Hailun ^{[1
]}

Yang, Lehe ^{[1
,2
,3
]}

Kang, Yanting ^{[1
,4
]}

Chen, Min ^{[1
]}

Lin, Shichong ^{[2
]}

Xiang, Youqun ^{[2
]}

Li, Caleb ^{[5
]}

Dai, Xuanxuan ^{[2
]}

Huang, Xiaoying ^{[2
]}

Liang, Guang ^{[1
]}

Zhao, Chengguang ^{[1
,3
]}

机构：

[1] Wenzhou Med Univ, Sch Pharmaceut Sci, Chem Biol Res Ctr, Chashan St, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Heart & Lung, Div Pulm Med, Wenzhou 325000, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Affiliated Yueqing Hosp, Dept Resp Med, Wenzhou, Zhejiang, Peoples R China

[4] Yichun Peoples Hosp, Dept Ultrasonog, Yichun, Jiangxi, Peoples R China

[5] Coffman High Sch, Dublin, OH USA

来源：

MOLECULAR CARCINOGENESIS | 2019年 / 58卷 / 04期

基金：

国家重点研发计划;

关键词：

alantolactone; EGFR; inhibitor; pancreatic cancer; STAT3; DE-NOVO RESISTANCE; LUNG-CANCER; FEEDBACK ACTIVATION; DRUG-RESISTANCE; GEMCITABINE; MUTATIONS; MECHANISM; ERLOTINIB; DOCKING; GROWTH;

D O I：

10.1002/mc.22951

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：565 / 576

页数：12

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