617: Combination Therapy with Plasmin-Cleaved Beta-2-Glycoprotein 1 and Docetaxel Inhibits the Growth of Orthotopically Implanted Tramp Murine Prostate Cancer Cells

2004 ◽  
Vol 171 (4S) ◽  
pp. 164-164
Author(s):  
Daniel D. Cohen ◽  
Weixin Lu ◽  
Alan J. Schroit
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Beta 2

scholarly journals An Anti-PSMA Immunotoxin Reduces Mcl-1 and Bcl2A1 and Specifically Induces in Combination with the BAD-Like BH3 Mimetic ABT-737 Apoptosis in Prostate Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1648
Author(s):  
Anie P. Masilamani ◽  
Viviane Dettmer-Monaco ◽  
Gianni Monaco ◽  
Toni Cathomen ◽  
Irina Kuckuck ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Target Cells ◽  
Prostate Cancer Cells ◽  
Mouse Xenograft Model ◽  
Synergistic Cytotoxicity ◽  
3D Spheroids

Background: Upregulation of anti-apoptotic Bcl-2 proteins in advanced prostate cancer leads to therapeutic resistance by prevention of cell death. New therapeutic approaches aim to target the Bcl-2 proteins for the restoration of apoptosis. Methods: The immunotoxin hD7-1(VL-VH)-PE40 specifically binds to the prostate specific membrane antigen (PSMA) on prostate cancer cells and inhibits protein biosynthesis. It was tested with respect to its effects on the expression of anti-apoptotic Bcl-2 proteins. Combination with the BAD-like mimetic ABT-737 was examined on prostate cancer cells and 3D spheroids and in view of tumor growth and survival in the prostate cancer SCID mouse xenograft model. Results: The immunotoxin led to a specific inhibition of Mcl-1 and Bcl2A1 expression in PSMA expressing target cells. Its combination with ABT-737, which inhibits Bcl-2, Bcl-xl, and Bcl-w, led to an induction of the intrinsic apoptotic pathway and to a synergistic cytotoxicity in prostate cancer cells and 3D spheroids. Furthermore, combination therapy led to a significantly prolonged survival of mice bearing prostate cancer xenografts based on an inhibition of tumor growth. Conclusion: The combination therapy of anti-PSMA immunotoxin plus ABT-737 represents the first tumor-specific therapeutic approach on the level of Bcl-2 proteins for the induction of apoptosis in prostate cancer.

Novel combination therapy of prostate cancer cells with arsenic trioxide and flutamide: An in-vitro study

2022 ◽  
Vol 74 ◽  
pp. 101684
Author(s):  
Akram Mirzaei ◽  
Mohammad Reza Akbari ◽  
Seyed Saeed Tamehri Zadeh ◽  
Fatemeh Khatami ◽  
Rahil Mashhadi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Arsenic Trioxide ◽  
In Vitro Study ◽  
Vitro Study ◽  
Prostate Cancer Cells

scholarly journals Combining Two Classes of Epigenetic Modifiers and Their Effect on Prostate Cancer Cells

2020 ◽  
Author(s):  
Mudassir K. Lodi ◽  
Ekaterine Goliadze ◽  
Masoud H. Manjili ◽  
Georgi Guruli
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Combination Therapy ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Annexin V ◽  
Prostate Cancer Cells ◽  
In Vivo Models ◽  
Apoptosis Rate ◽  
Epigenetic Modifiers

AbstractThe main objective of this experiment was to determine and study the effects of combining two epigenetic modifiers, 5-azacyticidine (5-AzaC) and SB939, on a RM-1 murine prostate cancer cell model. The effectiveness of this combination on prostate cancer cells has not been previously studied. The study was implemented on ex vivo cell models to gain a better understanding of the true effects of the combination therapy on prostate cancer cells. Two variations of the combination therapy were tested in this study, each with different concentrations of SB939 (100nm and 200nm).To determine the effectivity of the combination therapy on prostate cancer cells, three factors were measured: cell proliferation, cancer testis antigen (CTA) expression, and apoptosis rate. To measure cell proliferation, a cell proliferation assay was conducted, and absorption rate was measured through a 450 nm wavelength. CTA expression was measured through a quantitative polymerase chain reaction (quant-PCR). For this study, the expression rates of five CTAs were measured (TEX15, CEP55, CCNA1, P1A, SPA17). Apoptosis rate was measured through an Annexin-V assay, in which two markers, Annexin-V and 7-AAD, were used.We found that SB939 combined with 5-AzaC show highest efficacy compare to each drug alone in terms of inhibiting tumor cell proliferation, as well as inducing tumor cells apoptosis and enhancing tumor cell immunogenicity by the induction of the expression of CTAs. This combination proved to be effective in combating murine prostate cancer cells, and can potentially be effective within in vivo models due to its high toxicity to these cancer cells, and its ability to render prostate cancer more immunogenic.

Induction of protective immunity to RM-1 prostate cancer cells with ALVAC-IL-2/IL-12/TNF-α combination therapy

2006 ◽  
Vol 119 (11) ◽  
pp. 2632-2641 ◽  
Author(s):  
Julieann F. Grant ◽  
Toshihisa Iwasawa ◽  
Haley W. Sinn ◽  
D. Robert Siemens ◽  
Thomas S. Griffith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Protective Immunity ◽  
Prostate Cancer Cells ◽  
Tnf Α

scholarly journals γ-Tocotrienol and α-Tocopherol Ether Acetate Enhance Docetaxel Activity in Drug-Resistant Prostate Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 398
Author(s):  
Spencer Asay ◽  
Andrew Graham ◽  
Sydney Hollingsworth ◽  
Bradley Barnes ◽  
Richard V. Oblad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Cell Viability ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Statistical Technique ◽  
Chemotherapeutic Agents ◽  
Response Surfaces ◽  
Therapeutic Resistance ◽  
Prostate Cancer Cells

Prostate cancer is the second most commonly diagnosed cancer in men, and metastatic prostate cancer is currently incurable. Prostate cancer frequently becomes resistant to standard of care treatments, and the administration of chemotherapeutic drugs is often accompanied by toxic side effects. Combination therapy is one tool that can be used to combat therapeutic resistance and drug toxicity. Vitamin E (VE) compounds and analogs have been proposed as potential non-toxic chemotherapeutics. Here we modeled combination therapy using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize mixture compositions, to determine whether combinations of three chemotherapeutic agents: γ-tocotrienol (γ-T3), α-tocopherol ether acetate (α-TEA), and docetaxel (DOC), would prove more effective than docetaxel alone in the treatment of human prostate cancer cells. Response surfaces were generated for cell viability, and the optimal treatment combination for reducing cell viability was calculated. We found that a combination of 20 µM γ-T3, 30 µM α-TEA, and 25 nm DOC was most effective in the treatment of PC-3 cells. We also found that the combination of γ-T3 and α-TEA with DOC decreased the amount of DOC required to reduce cell viability in PC-3 cells and ameliorated therapeutic resistance in DOC-resistant PC-3 cells.

scholarly journals The Role of Crosstalk between AR3 and E2F1 in Drug Resistance in Prostate Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1094
Author(s):  
Jin Xu ◽  
Xi Yang ◽  
Dhanraj Deshmukh ◽  
Hegang Chen ◽  
Shengyun Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Cell Lines ◽  
Drug Combinations ◽  
Drug Resistant ◽  
Prostate Cancer Cells ◽  
Feedforward Loop ◽  
Underlying Mechanisms

Background: Drug resistance is one of the most prevalent causes of death in advanced prostate cancer patients. Combination therapies that target cancer cells via different mechanisms to overcome resistance have gained increased attention in recent years. However, the optimal drug combinations and the underlying mechanisms are yet to be fully explored. Aim and methods: The aim of this study is to investigate drug combinations that inhibit the growth of drug-resistant cells and determine the underlying mechanisms of their actions. In addition, we also established cell lines that are resistant to combination treatments and tested new compounds to overcome the phenomenon of double drug-resistance. Results: Our results show that the combination of enzalutamide (ENZ) and docetaxel (DTX) effectively inhibit the growth of prostate cancer cells that are resistant to either drug alone. The downregulation of transcription factor E2F1 plays a crucial role in cellular inhibition in response to the combined therapy. Notably, we found that the androgen receptor (AR) variant AR3 (a.k.a. AR-V7), but not AR full length (AR-FL), positively regulates E2F1 expression in these cells. E2F1 in turn regulates AR3 and forms a positive regulatory feedforward loop. We also established double drug-resistant cell lines that are resistant to ENZ+DTX combination therapy and found that the expression of both AR3 and E2F1 was restored in these cells. Furthermore, we identified that auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, overcame drug resistance and inhibited the growth of drug-resistant prostate cancer cells both in vitro and in vivo. Conclusion and significance: This proof-of-principle study demonstrates that targeting the E2F1/AR3 feedforward loop via a combination therapy or a multi-targeting drug could circumvent castration resistance in prostate cancer.

scholarly journals Zoledronic Acid Enhances the Chemotherapeutic Efficiency of 5-fluorouracil or Flutamide in Prostate Cancer Cells with Modulation of miR-382 and miR-18a Expression

2021 ◽  
Vol 72 (2) ◽  
pp. 102-118
Author(s):  
Amr M. Yehia ◽  
Mahmoud G. Eldeib ◽  
Ahmed M. Mohamadin ◽  
Mohammed M. El-Zahab
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Combination Therapy ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Health Concern ◽  
Prostate Cancer Cells ◽  
Chemotherapeutic Efficacy ◽  
Du145 Cells

Owing to a lack of appropriate therapeutic regimens, prostate cancer (PC) is a global health concern with a high incidence and mortality rate in elderly men. Combination treatment seems to have the highest clinical benefit and avoids unwanted side effects. The current study focused on the chemotherapeutic efficacy of Zoledronic acid (ZA) in combination with 5-fluorouracil (5-FU) or Flutamide on prostate cancer cells, as well as its effect on apoptosis. The MTT assay was used to determine the cytotoxic effect of Zoledronic acid (ZA), 5-FU, and flutamide on PC-3 and DU-145 cells, as well as the combined therapy of ZA with 5-FU or flutamide. Additionally, immunofluorescence staining analysis was used to assess changes in Bcl-2 and p53 expression. Furthermore, the western blotting method was extensively used to evaluate Bax, caspase 3, and cyclin D1. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the relative expression of miRNA-382 (miR-382) and miRNA-18a (miR-18a). Instead of (13.47, 8.23, and 9.42 μM) for PC-3 or (38.77, 17.6, and 8.47 μM) for DU145 cells, the combination therapy improved cytotoxicity with doses approximately half of IC50 (6.74, 4.12, and 7.07 μM) in PC-3 and (19.38, 8.8, and 6.33 μM) in DU145 cells for ZA, 5-FU, and flutamide, respectively. When compared to a single therapy, the combination therapy significantly up-regulated the pro-apoptotic Bax, cleaved caspase 3 and p53 levels while down-regulated the cyclin D1 and Bcl-2 expression. In addition, the combination therapy was linked to changes in miR-382 and miR-18a expression. Our findings suggest that combining ZA with 5-FU or flutamide improves chemotherapeutic efficacy against prostate cancer cells, at least in part by encouraging apoptosis and modulating miRNA expression, especially miR-382 and miR-18a.

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