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Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective：To investigate the mechanism of olaparib combined with enzalutamide in synergistically inhibiting the growth of prostate cancer cells. Methods：CCK -8 was used to determine the half -inhibitory concentrations of olaparib and enzalutamide in prostate cancer cell line C4-2，as well as the combined index of the two drugs. The effects of the combination of the two drugs on the proliferation and apoptosis of prostate cancer cells were verified by in vitro proliferation，clone formation experiments and flow cytometry. The accumulation of double - strand damagewas observed by immunofluorescence. Next - generation high - throughput sequencing of prostate cancer cells treated with olaparib and enzalutamide in combination and alone was used to explore the mechanism of the synergistic effect of the two drugs. The mRNA and protein expression levels of key genes in the synergistic pathway were detected by qRT - PCR and Western blot. Results：The combination index showed that the combination of olaparib and enzalutamide had strong synergistic effects in prostate cancer cell line C4-2. Compared with the single drug，the combined use of the two drugs significantly inhibited cell proliferation and cell cloning ability. Flow cytometry showed that the combination of the two drugs significantly promoted cell apoptosis compared with the single drug. Immunofluorescence showed that the double - strand damagewas significantly increased after the combination of the two drugs. Analysis of the results of next -generation high -throughput sequencing showed that the combination of the two drugs led to the activation of apoptosis and other pathways. Through the detection of mRNA and protein，it was found that the combination of the two drugs would lead to the high expression of the pro-apoptotic genes TNFAIP2 and TNFAIP8L1，and the low expression of the anti - apoptotic gene TNFAIP8. Conclusion：Olaparib combined with enzalutamide can promote the expression of pro-apoptotic genes TNFAIP2 and TNFAIP8L1 and inhibit the expression of anti-apoptotic gene TNFAIP8 to synergistically promote cell apoptosis and inhibit the growth of prostate cancer cells. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of nitrogen permease regulator like-2 (NPRL2) on the sensitivity of castration-resistant prostate cancer (CRPC) to olaparib. Methods Immunohistochemical staining of NPRL2 was performed in surgical specimens from the patients with benign prostatic hyperplasia (BPH), common prostate cancer (PCa) and CRPC. The expression of NPRL2 in the above tissues was observed and compared. Western blot assay was used to detect the protein level of NPRL2 in normal prostate epithelial cell line RWPE-1, prostate cancer cell line LNCaP and enzaliline-resistant castrated prostate cancer cell line LNPER. Overexpression and interference of NPRL2 were established by transfection of lentivirus into CRPC cells. The overexpression and interference efficiencies of NPRL2 were verified by real-time fluorescent PCR and Western blotting. ATM protein expression was detected by Western blotting. Cell proliferation and cytotoxicity were detected by CCK-8 assay, cell apoptosis was detected by flow cytometry, and invasion and migration were used with Transwell chamber test. Results Immunohistochemical assay showed that NPRL2 was highly expressed in the CRPC tissues. Western blotting showed that NPRL2 was down-regulated in RWPE-1 cells but highly expressed in LNCaP and LNPER cells. After successfully constructed a stable strain that overexpressed and interfered with NPRL2, qPCR and Western blotting showed that lentiviral transfection significantly increased and decreased the expression of NPRL2 at mRNA and protein levels, respectively(P < 0.01). And the results of CCK8 assay, flow cytometry and Transwell test indicated that silencing NPRL2 combined with olaparib treatment significantly inhibited cell growth, prevented cell invasion and metastasis, and promoted cell apoptosis when compared with the negative control group (P < 0.01). NPRL2 was positively correlated with ATM expression, and NPRL2 overexpression combined with olaparib treatment significantly enhanced ATM expression. Conclusion NPRL2 interference increases the sensitivity of CRPC cells to olaparib.

Objective To compare the efficacy and safety of olaparib in combination with pembrolizumab with pembrolizumab alone in second-line treatment for patients with extensive stage-small cell lung cancer (ES-SCLC) whose ages ranged from 40 to 80 years. Methods From March 2017 to October 2019, 21 patients with progressed or relapsed small cell lung cancer after standard first line treatment were enrolled in this study. The olaparib/pembrolizumab group (n=11) was treated by olaparib 300mg twice per day combined with pembrolizumab 200mg once every 3 weeks, while pembrolizumab group was treated by pembrolizumab alone. Results The objective response rate (ORR) of olaparib/pembrolizumab group and pembrolizumab group were 45.5% and 10.0%, respectively (P=0.149), and the disease control rate (DCR) were 81.8% and 70.0% (P=0.635). The median progression-free survival (PFS) were 5.93 months and 3.53 months (P=0.036), the median overall survival (OS) were 10.43 months and 8.43 months (P=0.063). The adverse reaction incidences of all grades were 90.9% and 70.0% (P=0.311), and the incidences of grade Ⅲ-Ⅴ including myelosuppression were 36.4% and 10.0% (P=0.311), gastrointestinal reaction were 9.1% and 10.0%, (P=1.000) and other immune-related adverse events were 18.2% and 30.0% (P=1.000). Further analysis showed the metastatic number (P=0.006), platinum sensitivity (P=0.036) and LDH level (P=0.022) significantly affected the ORR of olaparib/pembrolizumab therapy. Conclusion Our preliminary study indicates that olaparib combined with pembrolizumab is an efficient and safe second-line treatment therapy for patients with ES-SCLC. [ABSTRACT FROM AUTHOR]

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To investigate the effect of olaparib on melanoma cells and its mechanism. Methods: CCK8 was used to detect the viability of melanoma cells after being treated with olaparib at different concentrations. Western blot was used to detect expression of proteins related with apoptosis and cell cycle in melanoma cells treated with olaparib. Results: Compared with the control group, 5 滋M olaparib can inhibit the viability of melanoma cells (85.53± 2.593)%. And the inhibitory effect of olaparib on the viability of melanoma cells was stronger as its concentration doubling. The viability of melanoma cells were changed to (68.88 ± 1.484)%, (47.21± 1.759)%, (33.04± 1.261)%, (28.17± 1.731)% after the treatment of olaparib at 10 滋M, 20 滋M, 40 滋M, 80 滋M concentrations respectively. Olaparib treatment can promote the expression of apoptosis-related cleaved-PARP1 and inhibit the expression of cell cycle-related cyclin D1 in melanoma cells. Conclusion: Olaparib play a role in inhibiting the viability of melanoma cells by promoting the apoptosis and inhibiting the expression of cell cycle protein. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of olaparib in combination with pembrolizumab with pembrolizumab alone in second-line treatment for patients with extensive stage-small cell lung cancer (ES-SCLC) whose ages ranged from 40 to 80 years. Methods: From March 2017 to October 2019, 21 patients with progressed or relapsed small cell lung cancer after standard first line treatment were enrolled in this study. The olaparib/pembrolizumab group ( n =11) was treated by olaparib 300mg twice per day combined with pembrolizumab 200mg once every 3 weeks, while pembrolizumab group was treated by pembrolizumab alone. Results: The objective response rate (ORR) of olaparib/pembrolizumab group and pembrolizumab group were 45.5% and 10.0%, respectively ( P =0.149), and the disease control rate (DCR) were 81.8% and 70.0% ( P =0.635). The median progression-free survival (PFS) were 5.93 months and 3.53 months ( P =0.036), the median overall survival (OS) were 10.43 months and 8.43 months ( P =0.063). The adverse reaction incidences of all grades were 90.9% and 70.0% ( P =0.311), and the incidences of grade Ⅲ-Ⅴ including myelosuppression were 36.4% and 10.0% ( P =0.311), gastrointestinal reaction were 9.1% and 10.0%, ( P =1.000) and other immune-related adverse events were 18.2% and 30.0% ( P =1.000). Further analysis showed the metastatic number ( P =0.006), platinum sensitivity ( P =0.036) and LDH level ( P =0.022) significantly affected the ORR of olaparib/pembrolizumab therapy. Conclusion: Our preliminary study indicates that olaparib combined with pembrolizumab is an efficient and safe second-line treatment therapy for patients with ES-SCLC.