| INTRODUC TI ONOesophageal cancer is one of the most leading cause of mortality cancer worldwide, and oesophageal squamous cell carcinoma (ESCC) is the main type for oesophageal cancer arising from oesophageal epithelial cells. 1,2 The recent epidemiology showed that oesophageal cancer is one of the five most common cancers in China, especially in middle area of China, and attributed for about 1 396 000 people mortalities. 3 Despite the multiple efforts made in recent years, treatments for oesophageal cancer are still not satisfied and chemotherapy resistance has becoming a new challenge for its treatment.Therefore, it is important to reveal the mechanism of ESCC and improve the therapeutic effect of ESCC.Epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase, plays critical role in several solid cancers and its chemotherapy resistance regulation. 4 It is reported that about 40%-70% of patients with ESCC have presented with high levels of EGFR expression 5,6 and inhibiting the activity of EGFR might be promising to improve the outcome of patients with ESCC. Gefitinib is a wellknown orally active, reversible and selective EGFR inhibitor applied for ESCC treatment in clinic. 7,8 However, the resistance of gefitinib has become a new challenge for ESCC treatment with unclear mechanism. 9Long non-coding RNAs (lncRNAs) is a class of transcripts without coding capacity at a length of >200 nt and has reported to play critical roles in the pathogenesis and drug resistance of ESCC. 10,11
AbstractThis study aimed to explore the underlying mechanism of linc01014 in oesophagus cancer gefitinib resistance. Gefitinib-resistant oesophagus squamous cell carcinoma (ESCC gefitinibR) cell lines were constructed by using different gefitinib treatment in FLO-1, KYAE-1, TE-8 and TE-5 cell lines and confirmed by MTS50 and proliferation assays. Expression of linc01014 was overexpressed/silenced in FLO-1 cells followed by gefitinib treatment, and then, the apoptosis-associated markers Bax and Bcl-2, and PI3KCA in PI3K signalling pathway were determined using Western blotting. MST50 and morphology analyses showed that ESCC gefitinibR cell lines presented obvious gefitinib resistance than their parental ESCC cell lines. ESCC gefitinibR cell lines showed significantly higher proliferation abilities than their parental ESCC cell lines after treating with gefitinib. Overexpression of linc01014 significantly inhibited the apoptosis of FLO-1 cells induced by gefitinib and silencing linc01014 obviously promoted the apoptosis of FLO-1 cells induced by gefitinib. Silencing linc01014 could significantly increase the gefitinib chemotherapy sensitivity of oesophagus cancer via PI3K-AKT-mTOR signalling pathway.