| 朱家伦,王永斌,杨传周,等.二氯化锶联合阿帕替尼治疗80例前列腺癌骨转移的临床疗效及对癌细胞增殖和转移的影响[J].肿瘤学杂志,2022,28(10):847-854. |
| 二氯化锶联合阿帕替尼治疗80例前列腺癌骨转移的临床疗效及对癌细胞增殖和转移的影响 |
| Efficacy of 89SrCl2 Combined with Apatinib in Treatment of 80 Prostate Cancer Patients with Bone Metastases and Its Effect on Cancer Cell Proliferation and Invasion |
| 投稿时间：2022-01-10 |
| DOI：10.11735/j.issn.1671-170X.2022.10.B008 |
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| 中文关键词: 前列腺癌 骨转移 氯化锶 阿帕替尼 增殖 凋亡 转移 |
| 英文关键词:prostate cancer bone metastases strontium chloride apatinib proliferation apoptosis metastasis |
| 基金项目:云南省教育厅科学研究基金资助性项目（2019J1278） |
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| 中文摘要: |
| 摘 要：［目的］ 分析二氯化锶联合阿帕替尼治疗前列腺癌骨转移的临床疗效及对癌细胞增殖和转移的影响。［方法］ 选取2017年4月至2020年4月收治的前列腺癌骨转移患者80例，随机分为对照组（40例）和联合组（40例）。对照组单纯给予二氯化锶（89SrCl2）治疗，联合组采用89SrCl2联合阿帕替尼治疗。比较两组患者的临床疗效和不良反应发生率；记录两组患者治疗前后的骨转移灶数量、疼痛评分、Karnofsky评分和血清前列腺特异性抗原（PSA）含量的变化情况。同时，前列腺癌PC-3细胞分为空白对照组、89SrCl2处理组和89SrCl2联合阿帕替尼处理组。采用CCK-8、流式细胞术、Transwell和Western blot检测89SrCl2联合阿帕替尼对前列腺癌骨转移细胞PC-3的增殖、凋亡、侵袭、迁移和上皮间质转化（EMT）的影响。［结果］ 治疗后联合组的临床总有效率明显高于对照组（92.5% vs 72.5%；P<0.05）。治疗3个月后，两组患者的骨转移灶数量和止痛效果均优于治疗前（P<0.001），且患者经联合治疗后骨转移灶数量（4.09±0.42 vs 4.88±0.96）和疼痛评分（3.14±0.76 vs 4.31±0.84）均低于对照组（P<0.001），Karnofsky评分高于对照组（74.42±2.72 vs 67.46±3.25）。治疗后联合组患者的血清PSA水平低于对照组（17.25±6.62 vs 21.09±7.65；P<0.01）。同时，两组不良反应发生率比较差异无统计学意义（P>0.05）。相比于空白组，单纯89SrCl2处理后可显著抑制PC-3细胞增殖（72 h：0.85±0.07 vs 1.21±0.07）、侵袭（158.06±9.23 vs 231.85±15.52；P<0.001）、迁移（161.95±11.21 vs 257.14±17.35；P<0.001）、EMT（N-cadherin：0.55±0.06 vs 1.00±0.05；Vimentin：0.42±0.05 vs 1.00±0.06；E-cadherin：1.95±0.07 vs 1.00±0.06；P<0.001）以及诱导细胞凋亡（10.94±1.25 vs 1.96±1.05；P<0.001）。同时，89SrCl2联合阿帕替尼对PC-3细胞增殖（72 h：0.52±0.06 vs 0.85±0.07）、侵袭（45.32±7.48 vs 158.06±9.23；P<0.001）、迁移（53.17±8.31 vs 161.95±11.21；P<0.001）、EMT（N-cadherin：0.21±0.04 vs 0.55±0.06；Vimentin：0.12±0.04 vs 0.42±0.05；E-cadherin：3.86±0.08 vs 1.95±0.07；P<0.001）的抑制作用以及诱导细胞凋亡（23.64±2.52 vs 10.94±1.25）显著优于单纯89SrCl2组。［结论］ 89SrCl2联合阿帕替尼治疗前列腺癌骨转移临床疗效显著，安全性高，且可显著抑制癌细胞增殖和转移，值得临床推广使用。 |
| 英文摘要: |
| Abstract： ［Objective］ To analyze the clinical efficacy of 89SrCl2 combined with apatinib in treatment of prostate cancer patients with bone metastases and its effect on cancer cell proliferation and invasion. ［Methods］ A total of 80 patients with bone metastasis of prostate cancer admitted in Yunnan Cancer Hospital from April 2017 to April 2020 were randomly divided into the control group(n=40) and the combination treatment group(n=40). The control group was treated with 89SrCl2 alone， and the combination group was treated with 89SrCl2 combined with apatinib. The clinical efficacy and the incidence of adverse reactions were compared between the two groups. The number of bone metastases， pain score changes， Karnofsky score， and the level of prostate specific antigen(PSA) of the two groups before and after treatment were recorded. In study in vitro the cultured prostate cancer PC-3 cells were divided into blank control group， 89SrCl2 group， and 89SrCl2 combined with apatinib group. The effects of 89SrCl2 combined with apatinib on the proliferation， apoptosis， invasion， migration， and epithelial-mesenchymal transition(EMT) capacities of PC-3 were investigated. ［Results］ The total effective rate of combination treatment group was significantly higher than that in the control group(92.5% vs 72.5%， P<0.05). After three months of treatment， the number of bone metastases was reduced and pain score was decreased in both groups(P<0.001)， while the number of bone metastases in combination group was less(4.09±0.42 vs 4.88±0.96) and pain score was lower(3.14±0.76 vs 4.31±0.84) than those of the control group(P<0.001)； Meanwhile， the Karnofsky score was higher(74.42±2.72 vs 67.46±3.25) and the PSA level was lower(17.25±6.62 vs 21.09±7.65) than those in control group(both P<0.001). There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05). Treatment with 89SrCl2 alone significantly suppressed PC-3 cell proliferation(72h： 0.85±0.07 vs 1.21±0.07； P<0.01)， invasion(158.06±9.23 vs 231.85±15.52； P<0.001)， migration(161.95±11.21 vs 257.14±17.35； P<0.001)， and EMT(N-cadherin： 0.55±0.06 vs 1.00±0.05； Vimentin： 0.42±0.05 vs 1.00±0.06； E-cadherin： 1.95±0.07 vs 1.00±0.06； P<0.001) abilities， enhanced cell apoptosis(10.94±1.25 vs 1.96±1.05； P<0.001). The inhibitory effect of 89SrCl2 combined with apatinib on the proliferation(72 h： 0.52±0.06 vs 0.85±0.07)， invasion(45.32±7.48 vs 158.06±9.23)， migration(53.17±8.31 vs 161.95±11.21)， EMT(N-cadherin： 0.21±0.04 vs 0.55±0.06； Vimentin： 0.12±0.04 vs 0.42±0.05； E-cadherin： 3.86±0.08 vs 1.95±0.07)； and enhancing effect on apoptosis(23.64±2.52 vs 10.94±1.25) of PC-3 cells were significantly more marked than those of the 89SrCl2 alone group(P<0.001). ［Conclusion］ 89SrCl2 combined with alpatinib has a significant clinical efficacy for patients with prostate cancer bone metastasis with high safety. And in vitro study shows that it can significantly inhibit the proliferation， migration， invasion and EMT of prostate cancer cells. |
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