Liu Qi, Yang Weihong, Luo Ning, Liu Jie, Wu Yuliang, Ding Jinye, Li Caixia, Cheng Zhongping
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine, Shanghai, China.
J Cancer. 2020 May 18;11(15):4413-4420. doi: 10.7150/jca.41035. eCollection 2020.
: Immunotherapy including immune checkpoint blockade, cancer vaccines, and adoptive cell therapy. However, no immune therapies support ovarian cancer. It is not clear whether the neutrophils, the component of the immune system derived from umbilical cord blood play a role in inhibiting the progression of ovarian cancer. : We investigate the impact of LPS and IL-8 activated neutrophils derived from umbilical cord blood(UCB)on ovarian cancer progression. After co-culture LPS and IL-8 activated UCB-derived neutrophils with ovarian cancer cell line SKOV3 and OVCAR3, CCK8, Transwell assay, and Flow Cytometry was performed to detect cell proliferation, migration, invasion, and apoptosis of ovarian cancer cell lines SKOV3 and OVCAR3. Furthermore, RT-PCR and western blotting assay were used to analyze the mechanism of metastasis and apoptosis of ovarian cancer cell lines respectively to support previous function experiments. : We demonstrate LPS and IL-8 activated neutrophils derived from umbilical cord blood inhibit proliferation, invasion migration and promote apoptosis of SKOV3 and OVCAR3. Meanwhile, LPS and IL-8 activated UCB-derived neutrophils significantly decreased BAX and increased BCL2 expression in SKOV3 and OVCAR3 which account for the mechanism of apoptosis. Moreover, LPS and IL-8 activated UCB derived neutrophils significantly up-regulated E-cadherin and downregulated N-cadherin, MMP2 expression in SKOV3 and OVCAR3. : Taken together, these results approved that LPS and IL-8 activated neutrophils from UCB may be the novel strategy in immune therapy for ovarian cancer.
免疫疗法包括免疫检查点阻断、癌症疫苗和过继性细胞疗法。然而，尚无免疫疗法可用于支持卵巢癌治疗。目前尚不清楚源自脐带血的免疫系统组成部分中性粒细胞是否在抑制卵巢癌进展中发挥作用。
我们研究了脂多糖（LPS）和白细胞介素-8（IL-8）激活的脐带血来源中性粒细胞对卵巢癌进展的影响。将LPS和IL-8激活的脐带血来源中性粒细胞与卵巢癌细胞系SKOV3和OVCAR3共培养后，进行CCK8、Transwell实验和流式细胞术检测卵巢癌细胞系SKOV3和OVCAR3的细胞增殖、迁移、侵袭及凋亡情况。此外，分别采用逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法分析卵巢癌细胞系转移和凋亡的机制，以支持先前的功能实验。
我们证明，LPS和IL-8激活的脐带血来源中性粒细胞可抑制SKOV3和OVCAR3的增殖、侵袭和迁移，并促进其凋亡。同时，LPS和IL-8激活的脐带血来源中性粒细胞显著降低SKOV3和OVCAR3中BAX的表达并增加BCL2的表达，这解释了凋亡的机制。此外，LPS和IL-8激活的脐带血来源中性粒细胞显著上调SKOV3和OVCAR3中E-钙黏蛋白的表达，并下调N-钙黏蛋白、基质金属蛋白酶2（MMP2）的表达。
综上所述，这些结果证实，LPS和IL-8激活的脐带血来源中性粒细胞可能是卵巢癌免疫治疗的新策略。
