Docetaxel‐resistant prostate cancer cells become sensitive to gemcitabine due to the upregulation of ABCB1

Seo, Ho Kyung; Lee, Sang‐Jin; Kwon, Whi‐An; Jeong, Kyung‐Chae

doi:10.1002/pros.23946

Cited by 15 publications

(9 citation statements)

References 41 publications

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“…Based on the PSA response rate of 55% and radiologic response rate of 82%, one could expect that advanced PCa treatment may build upon combined therapy with GEM. Increased sensitivity to GEM was supposed to be associated with the upregulation of ABCB1, which in contrast played a pivotal role in the development of docetaxel resistance [55]. Even though it is still not clear whether docetaxel‐resistant patients could benefit from GEM therapy, a recent study has demonstrated that GEM may be beneficial to effectively induce tumor regression in the DR CRPC model.…”

Section: Discussionmentioning

confidence: 99%

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel‐resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

et al. 2020

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candidate SCH900776. MU380 alone or in combination with GEM significantly reduced spheroid size and increased apoptosis in all patient-derived xenograft 3D cultures, with a higher impact in DR models. Combined treatment induced premature mitosis from G1 phase resulting in the mitotic catastrophe as a prestage of apoptosis. Finally, treatment by MU380 alone, or in combination with GEM, significantly inhibited tumor growth of both PC339-DOC and PC346C-DOC xenograft models in mice. Taken together, our data suggest that metabolically robust and selective CHK1 inhibitor MU380 can bypass docetaxel resistance and improve the effectiveness of GEM in DR mCRPC models. This approach might allow for dose reduction of GEM and thereby minimize undesired toxicity and may represent a therapeutic option for patients with incurable DR mCRPC.

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Section: Discussionmentioning

confidence: 99%

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel‐resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

et al. 2020

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“…EO771 mouse mammary tumor cells (CH3 BioSystems, Amherst, NY, USA), 4T1.2 mouse mammary tumor cells (obtained from Dr. R. Anderson at Peter MacCallum Cancer Institute, Melbourne, Australia), PANC-1 human pancreatic cancer cells (ATCC), and MCF-7 human estrogen receptor (ER)-positive breast cancer cells (ATCC) were cultured in DMEM (MT10013CV, Thermo Fisher Scientific). TRAMP-C2ras prostate tumor cells (ATCC) were cultured in DMEM/F-12 13 , and MDA-MB-231 human estrogen receptor (ER)-negative breast cancer cells and PC-3 human prostate cancer cells (ATCC) were cultured in RPMI-1640 (15040CV, Corning, Glendale, Arizona, USA) 14 , 15 . As non-tumor control cells, two epithelium lines (KTB36 and KTB6, obtained from Dr. H. Nakshatri, Indiana University) with the breast epithelial origin were cultured in F12-DMEM (low glucose) in a 3:1 ratio.…”

Section: Methodsmentioning

confidence: 99%

Generation of the tumor-suppressive secretome from tumor cells

Liu¹,

Sun²,

Li³

et al. 2021

Theranostics

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Rationale : The progression of cancer cells depends on the soil and building an inhibitory soil might be a therapeutic option. We previously created tumor-suppressive secretomes by activating Wnt signaling in MSCs. Here, we examined whether the anti-tumor secretomes can be produced from tumor cells. Methods: Wnt signaling was activated in tumor cells by overexpressing β-catenin or administering BML284, a Wnt activator. Their conditioned medium (CM) was applied to cancer cells or tissues, and the effects of CM were evaluated. Tumor growth in the mammary fat pad and tibia in C57BL/6 female mice was also evaluated through μCT imaging and histology. Whole-genome proteomics analysis was conducted to determine and characterize novel tumor-suppressing proteins, which were enriched in CM. Results: The overexpression of β-catenin or the administration of BML284 generated tumor-suppressive secretomes from breast, prostate and pancreatic cancer cells. In the mouse model, β-catenin-overexpressing CM reduced tumor growth and tumor-driven bone destruction. This inhibition was also observed with BML284-treated CM. Besides p53 and Trail, proteomics analysis revealed that CM was enriched with enolase 1 (Eno1) and ubiquitin C (Ubc) that presented notable tumor-suppressing actions. Importantly, Eno1 immunoprecipitated CD44, a cell-surface adhesion receptor, and its silencing suppressed Eno1-driven tumor inhibition. A pan-cancer survival analysis revealed that the downregulation of MMP9, Runx2 and Snail by CM had a significant impact on survival outcomes ( p < 0.00001). CM presented a selective inhibition of tumor cells compared to non-tumor cells, and it downregulated PD-L1, an immune escape modulator. Conclusions: The tumor-suppressive secretome can be generated from tumor cells, in which β-catenin presented two opposing roles, as an intracellular tumor promoter in tumor cells and a generator of extracellular tumor suppressor in CM. Eno1 was enriched in CM and its interaction with CD44 was involved in Eno1's anti-tumor action. Besides presenting a potential option for treating primary cancers and metastases, the result indicates that aggressive tumors may inhibit the growth of less aggressive tumors via tumor-suppressive secretomes.

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“…In addition, the results also showed that mutated TNXB only existed in the low-expression group of PRAD, while a high expression level of TNXB is correlated with a good survival prognosis in many cancers ( 61 ). Similarly, mutated ABCB1 was also found only in the low-expression group of PRAD, and it has been widely identified to take part in drug resistance of PRAD patients ( 62 – 64 ). Not only did ZNF419 employ mutated genes to participate in tumorigenesis and tumor progression, but epigenetic regulation also played an indispensable role.…”

Section: Discussionmentioning

confidence: 98%

A pan-cancer analysis of the oncogenic role of zinc finger protein 419 in human cancer

et al. 2022

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BackgroundAs a ferroptosis-related gene, the polymorphism of zinc finger protein 419 (ZNF419) at the splice donor site may generate renal cell carcinoma-associated novel minor histocompatibility antigen ZAPHIR. However, the role of ZNF419 in prognosis and immunology in human tumors remains largely unknown. This study aimed to visualize the prognostic landscape of ZNF419 at pan-cancer level and explore the relationship between ZNF419 expression and the tumor immune microenvironment.MethodPan-cancer and mutation data were downloaded from TCGA databases and analyzed through R (version 3.6.4) and its suitable packages. Differential ZNF419 expression and prognosis were analyzed. Correlations with ferroptosis-related genes, pathway analysis, tumor stemness, heterogeneity, mutation landscape, and RNA modifications were also explored. The relationships between ZNF419 expression and tumor immunity were investigated through the TIMER and ESTIMATE methods.ResultZNF419 was differentially expressed between tumor and normal samples and was associated with overall survival, disease-specific survival and progression-free interval for STES, KIRC, LIHC, LUSC, PRAD, and BLCA. We found the interaction between ZNF419 and FANCD2 might involve in ferroptosis in pan-cancer level. In addition, the mutation frequencies of STES, KIRC, LIHC, LUSC, PRAD, and BLCA were 1.5%, 0.3%, 0.3%, 1.9%, 0.2%, and 0.7%, respectively. We detected that the expression of ZNF419 was closely correlated with most immune checkpoint genes and immune regulatory genes. Furthermore, we found that the ZNF419 expression level was negatively related to the immune score in the six cancers mentioned above. The expression of ZNF419 was significantly associated with various infiltrating immune cells, such as CD4+ T cells, CD8+ T cells, and macrophages in patients with KIRC, PRAD, and LUSC but was only significantly related to macrophages in BLCA patients.ConclusionZNF419 might serve as a potential prognostic and immunological pan-cancer biomarker, especially for KIRC, LIHC, LUSC, PRAD, and BLCA.

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Docetaxel‐resistant prostate cancer cells become sensitive to gemcitabine due to the upregulation of ABCB1

Cited by 15 publications

References 41 publications

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel‐resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel‐resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

Generation of the tumor-suppressive secretome from tumor cells

A pan-cancer analysis of the oncogenic role of zinc finger protein 419 in human cancer

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