Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer
Patient-derived xenograft models reportedly represent original tumor morphology and gene mutation profiles. In addition, patient-derived xenografts are expected to recapitulate the parental tumor drug responses. In this study, we analyzed the pathways involved in gemcitabine resistance using patient...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/10/1396 |
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| author | Erica Yada Rika Kasajima Atsushi Niida Seiya Imoto Satoru Miyano Yohei Miyagi Tetsuro Sasada Satoshi Wada |
| author_facet | Erica Yada Rika Kasajima Atsushi Niida Seiya Imoto Satoru Miyano Yohei Miyagi Tetsuro Sasada Satoshi Wada |
| author_sort | Erica Yada |
| collection | DOAJ |
| description | Patient-derived xenograft models reportedly represent original tumor morphology and gene mutation profiles. In addition, patient-derived xenografts are expected to recapitulate the parental tumor drug responses. In this study, we analyzed the pathways involved in gemcitabine resistance using patient-derived xenograft models of pancreatic cancer. The patient-derived xenograft models were established using samples from patients with pancreatic cancer. The models were treated with gemcitabine to better understand the mechanism of resistance to this anti-cancer drug. We performed comparative gene analysis through the next-generation sequencing of tumor tissues from gemcitabine-treated or non-treated patient-derived xenograft mice and gene set enrichment analysis to analyze mRNA profiling data. Pathway analysis of gemcitabine-treated patient-derived xenografts disclosed the upregulation of multiple gene sets and identified several specific gene pathways that could potentially be related to gemcitabine resistance in pancreatic cancer. Further, we conducted an in vitro analysis to validate these results. The mRNA expression of cytochrome P450 1B1 and cytochrome P450 2A6 was upregulated in a concentration-dependent manner following gemcitabine treatment. Moreover, the sensitivity to gemcitabine increased, and viable cells were decreased by the cytochrome P450 1B1 inhibitor, indicating that the cytochrome P450 1B1 pathway may be related to gemcitabine resistance in pancreatic cancer. |
| first_indexed | 2024-03-10T06:42:17Z |
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| id | doaj.art-42d60ee7078340bcba2fa833e48b455c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T06:42:17Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-42d60ee7078340bcba2fa833e48b455c2023-11-22T17:31:15ZengMDPI AGBiomedicines2227-90592021-10-01910139610.3390/biomedicines9101396Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic CancerErica Yada0Rika Kasajima1Atsushi Niida2Seiya Imoto3Satoru Miyano4Yohei Miyagi5Tetsuro Sasada6Satoshi Wada7Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, JapanMolecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, JapanDivision of Health Medical Computational Science, Health Intelligence Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, JapanDivision of Health Medical Data Science, Health Intelligence Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, JapanDivision of Health Medical Computational Science, Health Intelligence Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, JapanMolecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, JapanDepartment of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, JapanDepartment of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, JapanPatient-derived xenograft models reportedly represent original tumor morphology and gene mutation profiles. In addition, patient-derived xenografts are expected to recapitulate the parental tumor drug responses. In this study, we analyzed the pathways involved in gemcitabine resistance using patient-derived xenograft models of pancreatic cancer. The patient-derived xenograft models were established using samples from patients with pancreatic cancer. The models were treated with gemcitabine to better understand the mechanism of resistance to this anti-cancer drug. We performed comparative gene analysis through the next-generation sequencing of tumor tissues from gemcitabine-treated or non-treated patient-derived xenograft mice and gene set enrichment analysis to analyze mRNA profiling data. Pathway analysis of gemcitabine-treated patient-derived xenografts disclosed the upregulation of multiple gene sets and identified several specific gene pathways that could potentially be related to gemcitabine resistance in pancreatic cancer. Further, we conducted an in vitro analysis to validate these results. The mRNA expression of cytochrome P450 1B1 and cytochrome P450 2A6 was upregulated in a concentration-dependent manner following gemcitabine treatment. Moreover, the sensitivity to gemcitabine increased, and viable cells were decreased by the cytochrome P450 1B1 inhibitor, indicating that the cytochrome P450 1B1 pathway may be related to gemcitabine resistance in pancreatic cancer.https://www.mdpi.com/2227-9059/9/10/1396gemcitabinePDX modelpancreatic cancerpatient-derived xenograftRNA sequencing |
| spellingShingle | Erica Yada Rika Kasajima Atsushi Niida Seiya Imoto Satoru Miyano Yohei Miyagi Tetsuro Sasada Satoshi Wada Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer Biomedicines gemcitabine PDX model pancreatic cancer patient-derived xenograft RNA sequencing |
| title | Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer |
| title_full | Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer |
| title_fullStr | Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer |
| title_full_unstemmed | Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer |
| title_short | Possible Role of Cytochrome P450 1B1 in the Mechanism of Gemcitabine Resistance in Pancreatic Cancer |
| title_sort | possible role of cytochrome p450 1b1 in the mechanism of gemcitabine resistance in pancreatic cancer |
| topic | gemcitabine PDX model pancreatic cancer patient-derived xenograft RNA sequencing |
| url | https://www.mdpi.com/2227-9059/9/10/1396 |
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