Key Laboratory of Tropical Translational Medicine of Ministry of Education and School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, 571199, Hainan, China.
Parasitol Res. 2020 Nov;119(11):3705-3718. doi: 10.1007/s00436-020-06872-4. Epub 2020 Sep 8.
Excretory-secretory products (ESPs) of parasitic helminths are well known to exert immunostimulation and immunomodulation in hosts. Immune regulation plays a key role in anti-tumour therapy. The present study explored the anti-tumour effect of ESPs released by Angiostrongylus cantonensis. In Hepa1-6 mouse tumour models, ESPs significantly reduced tumour growth. Tumour-bearing mice treated with ESPs had significantly higher CD3, CD4, and CD8 T cell counts than those treated with Freund's adjuvant. In vitro, human hepatocarcinoma HepG2 cells, human lung cancer A549 cells, and normal human liver HL-7702 cells were co-incubated with ESPs for 24 h and 48 h. ESPs significantly accelerated HepG2 apoptosis but had no inhibitory effect on the proliferation of A549 and HL-7702 cells. Apoptotic HepG2 cells displayed condensed nuclei, apoptotic bodies, and swollen endoplasmic reticulum (ER). Expression of the endoplasmic reticulum stress (ERS)-related factors activating transcription factor 6 (ATF6) and C/EBP-homologous protein (CHOP) in HepG2 cells increased with increasing ESP concentration and treatment time. Calreticulin (CRT) is a key effector protein of ESPs, and recombinant calreticulin (rCRT) was produced in BL21 Escherichia coli (E. coli). In contrast to ESPs, rCRT markedly reduced the proliferation of HepG2 cells. The expression levels of ATF6 and CHOP in HepG2 cells treated with 30 μg/mL rCRT significantly increased at 48 h. Notably, these findings synergistically suggest that ESPs and rCRT are promising candidates for anti-tumour immunotherapy.
寄生虫旋毛虫的排泄分泌产物（ESPs）在宿主体内具有免疫刺激和免疫调节作用。免疫调节在抗肿瘤治疗中起着关键作用。本研究探讨了广东住血线虫 ESPs 的抗肿瘤作用。在 Hepa1-6 小鼠肿瘤模型中，ESPs 显著抑制肿瘤生长。与弗氏佐剂处理的肿瘤小鼠相比，用 ESPs 处理的肿瘤小鼠的 CD3、CD4 和 CD8 T 细胞计数明显更高。体外，用人肝癌 HepG2 细胞、人肺癌 A549 细胞和正常人肝 HL-7702 细胞与 ESPs 共孵育 24 和 48 小时。ESPs 显著加速 HepG2 细胞凋亡，但对 A549 和 HL-7702 细胞的增殖没有抑制作用。凋亡的 HepG2 细胞显示出核浓缩、凋亡小体和扩张的内质网（ER）。随着 ESP 浓度和处理时间的增加，HepG2 细胞中内质网应激（ERS）相关因子激活转录因子 6（ATF6）和 C/EBP 同源蛋白（CHOP）的表达增加。钙网蛋白（CRT）是 ESPs 的关键效应蛋白，在 BL21 大肠杆菌（E. coli）中产生重组钙网蛋白（rCRT）。与 ESPs 相反，rCRT 显著降低 HepG2 细胞的增殖。用 30 μg/ml rCRT 处理的 HepG2 细胞中 ATF6 和 CHOP 的表达水平在 48 小时时显著增加。值得注意的是，这些发现协同表明，ESPs 和 rCRT 是抗肿瘤免疫治疗的有前途的候选物。
