核梭杆菌内毒素上调IL-6/p-STAT3信号通路参与结直肠癌发生

Fusobacterium nucleatum endotoxin upregulates the IL-6/p-STAT3 signaling pathway and participates in the development colorectal cancer

目的:探索具核梭杆菌(F.nucleatum)内毒素通过上调白介素-6(IL-6)/磷酸化STAT3(p-STAT3)信号通路对结直肠癌(colorectal cancer,CRC)发生的影响。方法:采用荧光原位杂交检测42例CRC组织中F.nucleatum的感染率;采用免疫组织化学法检测F.nucleatum阳性及阴性CRC组织中IL-6/STAT3的表达;用F.nucleatum内毒素干预结肠癌SW480细胞,Western-blot检测IL-6/p-STAT3的表达。结果:F.nucleatum在CRC组织中的感染率为69.0%(29/42)。F.nucleatum阳性CRC组织中IL-6(t=4.22,P<0.05)及STAT3蛋白(t=5.58,P<0.05)的表达明显高于F.nucleatum阴性CRC组织。F.nucleatum内毒素能明显增强结肠癌细胞株IL-6(t=-1.79~20.44,P<0.05)及磷酸化STAT3(p-STAT3)蛋白(t=-0.85^-16.53,P<0.05)的表达。结论 :F.nucleatum在CRC中具有较高的感染率,其内毒素可激活CRC的IL-6/p-STAT3信号通路,参与CRC的发生。

Objective： To investigate the effect of Fusobacterium nucleatum （F. nucleatum） endotoxin on the development of colorectal cancer （CRC） by upregulating the interleukin-6 （IL-6）/phosphorylated signal transducer and activator of transcription 3 （p-STAT3） signaling pathway. Methods： Fluorescence in situ hybridization was performed to measure the infection rate of F. nucleatum in 42 CRC tissue samples. Immunohistochemistry was used to measure the expression of IL-6/signal transducer and activator of transcription 3 （STAT3） in CRC tissue samples with or without F. nucleatum. The CRC SW480 ceils were treated with F. nucleatum endotoxin, and then Western blot was used to measure the expression of IL-6/p-STAT3. Results： The infection rate of F. nucleatum in CRC tissue samples was 69.0% （29/42）. The CRC tissue samples with F. nucleatum had significantly higher protein expression of IL-6 and STAT3 than those without F. nucleatum （t = 4.22 and 5.58, both P 〈 0.05）. F. nucleatum endotoxin significantly increased the protein expression of IL-6 （t = -1.79 to -20.44, P 〈 0.05） and p- STAT3 （t = -0.85 to -16.53, P 〈 0.05） in CRC SW480 ceils. Conclusions： There is a high infection rate of F. nucleatum in CRC, and its endotoxin activates the IL-6/p-STAT3 signaling pathway and thus participates in the development of CRC.