Ovarian cancer is the 5th leading cause of cancer-related mortality in women. Seventy-five percent of ovarian cancer patients present in advanced stages, and receive cytoreductive surgery and adjuvant chemotherapy. Ho...Ovarian cancer is the 5th leading cause of cancer-related mortality in women. Seventy-five percent of ovarian cancer patients present in advanced stages, and receive cytoreductive surgery and adjuvant chemotherapy. However, within 2 years 65% of these patients relapse and thereafter only receive palliative care. Novel therapies based on the biology of these cancers are urgently needed. The opioid growth factor (OGF)-OGF receptor (OGFr) axis is an endogenous opioid system known to inhibit proliferation of human ovarian cancer cells in tissue culture, but does not affect cell survival. The present study determined whether OGF in combination with standard of care chemotherapy, provides an inhibitory effect on the growth of human ovarian cancer cells in vitro. In addition, this investigation assessed whether OGF biotherapy, alone or in combination with taxol or cisplatin, inhibits tumor growth in mice with xenografts of ovarian cancer. The combination of OGF (10–6 M) with taxol (10–9 M or 10–10 M) or cisplatin (0.01 ug/ml or 0.001 ug/ml) markedly reduced cell number and DNA synthesis in vitro to a greater extent than individual compounds. OGF, but not taxol or cisplatin, altered growth in an opioid receptor mediated and reversible manner. Female nu/nu mice inoculated subcutaneously with SKOV-3 cells, and treated with OGF (10 mg/kg) for 5 weeks commencing at the time tumors became measurable, had tumor volumes and weight that were reduced by up to 50% from animals receiving saline. The combination of OGF with taxol (3 mg/kg, weekly) or cisplatin (4 mg/kg, weekly for 2 weeks) for 37 days reduced tumor volumes and weight in contrast to mice receiving individual agents alone. Moreover, OGF treatment in mice receiving cisplatin provided protection against the weight loss associated with cisplatin alone. All treatments suppressed DNA synthesis and angiogenesis, whereas exposure to taxol or cisplatin, but not OGF, induced apoptosis. Additive inhibitory effects on DNA synthesis and angiogenesis were recorded in animals展开更多
目的探讨阿片类生长因子受体假基因1(OGFRP1)对卵巢癌细胞增殖、侵袭和迁移的影响及其作用机制。方法选取120例卵巢癌患者癌组织及正常卵巢组织,实时荧光定量PCR(RT-qPCR)检测OGFRP1和miR-665表达水平;将A2780细胞分为空白(PBS)组、si-N...目的探讨阿片类生长因子受体假基因1(OGFRP1)对卵巢癌细胞增殖、侵袭和迁移的影响及其作用机制。方法选取120例卵巢癌患者癌组织及正常卵巢组织,实时荧光定量PCR(RT-qPCR)检测OGFRP1和miR-665表达水平;将A2780细胞分为空白(PBS)组、si-NC组、si-OGFRP1组、miR-NC组、miR-665组、si-OGFRP1+anti-miR-NC组、si-OGFRP1+anti-miR-665组。四甲基偶氮唑盐比色法(MTT)检测细胞存活率;Transwell检测细胞迁移和侵袭;双荧光素酶报告实验检测OGFRP1和miR-665的靶向关系。结果与正常卵巢组织相比,卵巢癌组织中OGFRP1表达水平升高(2.75±0.27 vs 1.00±0.09),miR-665表达水平降低(0.51±0.05 vs 1.00±0.08)(均P<0.05)。抑制OGFRP1表达或过表达miR-665后,卵巢癌A2780细胞的活性、细胞迁移与侵袭数均降低(均P<0.05)。双荧光素酶报告实验结果显示,OGFRP1靶向调控miR-665;抑制miR-665和OGFRP1表达后,卵巢癌A2780细胞活性升高,迁移、侵袭细胞数增加(P<0.05)。结论抑制OGFRP1表达可抑制卵巢癌A2780细胞增殖、迁移和侵袭,其机制可能与上调miR-665有关。展开更多
文摘Ovarian cancer is the 5th leading cause of cancer-related mortality in women. Seventy-five percent of ovarian cancer patients present in advanced stages, and receive cytoreductive surgery and adjuvant chemotherapy. However, within 2 years 65% of these patients relapse and thereafter only receive palliative care. Novel therapies based on the biology of these cancers are urgently needed. The opioid growth factor (OGF)-OGF receptor (OGFr) axis is an endogenous opioid system known to inhibit proliferation of human ovarian cancer cells in tissue culture, but does not affect cell survival. The present study determined whether OGF in combination with standard of care chemotherapy, provides an inhibitory effect on the growth of human ovarian cancer cells in vitro. In addition, this investigation assessed whether OGF biotherapy, alone or in combination with taxol or cisplatin, inhibits tumor growth in mice with xenografts of ovarian cancer. The combination of OGF (10–6 M) with taxol (10–9 M or 10–10 M) or cisplatin (0.01 ug/ml or 0.001 ug/ml) markedly reduced cell number and DNA synthesis in vitro to a greater extent than individual compounds. OGF, but not taxol or cisplatin, altered growth in an opioid receptor mediated and reversible manner. Female nu/nu mice inoculated subcutaneously with SKOV-3 cells, and treated with OGF (10 mg/kg) for 5 weeks commencing at the time tumors became measurable, had tumor volumes and weight that were reduced by up to 50% from animals receiving saline. The combination of OGF with taxol (3 mg/kg, weekly) or cisplatin (4 mg/kg, weekly for 2 weeks) for 37 days reduced tumor volumes and weight in contrast to mice receiving individual agents alone. Moreover, OGF treatment in mice receiving cisplatin provided protection against the weight loss associated with cisplatin alone. All treatments suppressed DNA synthesis and angiogenesis, whereas exposure to taxol or cisplatin, but not OGF, induced apoptosis. Additive inhibitory effects on DNA synthesis and angiogenesis were recorded in animals
文摘目的探讨阿片类生长因子受体假基因1(OGFRP1)对卵巢癌细胞增殖、侵袭和迁移的影响及其作用机制。方法选取120例卵巢癌患者癌组织及正常卵巢组织,实时荧光定量PCR(RT-qPCR)检测OGFRP1和miR-665表达水平;将A2780细胞分为空白(PBS)组、si-NC组、si-OGFRP1组、miR-NC组、miR-665组、si-OGFRP1+anti-miR-NC组、si-OGFRP1+anti-miR-665组。四甲基偶氮唑盐比色法(MTT)检测细胞存活率;Transwell检测细胞迁移和侵袭;双荧光素酶报告实验检测OGFRP1和miR-665的靶向关系。结果与正常卵巢组织相比,卵巢癌组织中OGFRP1表达水平升高(2.75±0.27 vs 1.00±0.09),miR-665表达水平降低(0.51±0.05 vs 1.00±0.08)(均P<0.05)。抑制OGFRP1表达或过表达miR-665后,卵巢癌A2780细胞的活性、细胞迁移与侵袭数均降低(均P<0.05)。双荧光素酶报告实验结果显示,OGFRP1靶向调控miR-665;抑制miR-665和OGFRP1表达后,卵巢癌A2780细胞活性升高,迁移、侵袭细胞数增加(P<0.05)。结论抑制OGFRP1表达可抑制卵巢癌A2780细胞增殖、迁移和侵袭,其机制可能与上调miR-665有关。
