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背景与目的非小细胞肺癌(non-small cell lung cancer,NSCLC)是当今世界上发病率和死亡率最高的恶性肿瘤之一,而表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKI)整体有效率为30%-40%,无进展生存期(progression-free survival,PFS)为12个月。但EGFR-TKI在临床中的耐药现象也很普遍,严重影响了其抑瘤作用。因此,克服耐药、寻找一种新的与肺癌耐药相关的预后因子势在必行。本研究旨在通过体内外实验探讨DNA结合抑制因子1(differentiation inhibitory factor 1,ID1)与NSCLCEGFR-TKI耐药之间的关系,看其是否有统计学意义,并初步探讨其机制。方法免疫组化(immunohistochemistry,IHC)检测手术标本(肺癌组织和癌旁组织)1D1的表达;q RT-PCR、Western-blot检测并比较肺癌细胞敏感株与耐药株中ID1的表达变化;MTT检测吉非替尼对ID1慢病毒载体处理肺癌细胞的细胞增殖情况,将肺癌细胞接种至裸鼠腋下,待肿瘤生长至一定体积使用吉非替尼治疗,估算肿瘤体积。结果 ID1在肺癌组织中的表达明显高于正常组织(P<0.05);ID1的表达与NSCLC EGFR-TKI耐药呈正相关(P<0.05)。结论 ID1在NSCLC中高表达,并且参与了NSCLC EGFRTKI的耐药,其机制可能与STAT3磷酸化程度增加有关。
Background and objective Non-small cell lung cancer (NSCLC) is one of the most malignant tumors in the world with the highest morbidity and mortality. However, epidermal growth factor receptor-epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) overall response rate was 30% -40%, progression-free survival (PFS) was 12 months. However, EGFR-TKI in clinical resistance phenomenon is also very common, seriously affecting its antitumor effect. Therefore, to overcome the resistance, to find a new prognostic factor associated with lung cancer resistance is imperative. This study aimed to explore the relationship between the DNA inhibitory factor 1 (ID1) and the drug resistance of NSCLC EGFR-TKI in vitro and in vivo and to see if there is statistical significance and to explore its mechanism. Methods Immunohistochemistry (IHC) was used to detect the expression of 1D1 in surgical specimens (lung cancer tissues and paracancerous tissues). The expression of ID1 in sensitive and resistant strains of lung cancer cells was detected by q RT-PCR and Western-blot. MTT Detection of gefitinib on ID1 lentiviral vector treatment of lung cancer cell proliferation, lung cancer cells were seeded into the armpit of nude mice until the tumor growth to a certain volume using gefitinib treatment to estimate the tumor volume. Results The expression of ID1 in lung cancer tissues was significantly higher than that in normal tissues (P <0.05). The expression of ID1 was positively correlated with EGFR-TKI resistance in NSCLC (P <0.05). Conclusion ID1 is highly expressed in NSCLC and is involved in the resistance of EGFRTKI in NSCLC. The mechanism may be related to the increased phosphorylation of STAT3.