Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway
The platelet-activating factor receptor (PAFR) is a key molecule that participates in intracellular signaling pathways, including regulating the activation of kinases. It is involved in cancer progression, but the detailed mechanism of its chemosensitivity is unknown. The purpose of the current stud...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/24/6299 |
| _version_ | 1797506384462348288 |
|---|---|
| author | Kohei Kawasaki Atsushi Kasamatsu Toshiaki Ando Tomoaki Saito Takafumi Nobuchi Ryunosuke Nozaki Manabu Iyoda Katsuhiro Uzawa |
| author_facet | Kohei Kawasaki Atsushi Kasamatsu Toshiaki Ando Tomoaki Saito Takafumi Nobuchi Ryunosuke Nozaki Manabu Iyoda Katsuhiro Uzawa |
| author_sort | Kohei Kawasaki |
| collection | DOAJ |
| description | The platelet-activating factor receptor (PAFR) is a key molecule that participates in intracellular signaling pathways, including regulating the activation of kinases. It is involved in cancer progression, but the detailed mechanism of its chemosensitivity is unknown. The purpose of the current study was to elucidate the mechanism regulating cisplatin (CDDP) sensitivity through PAFR functions in oral squamous cell carcinoma (OSCC). We first analyzed the correlation between PAFR expression and CDDP sensitivity in seven OSCC-derived cell lines based upon cell viability assays. Among them, we isolated 2 CDDP-resistant cell lines (Ca9-22 and Ho-1-N-1). In addition to conducting PAFR-knockdown (si<i>PAFR</i>) experiments, we found that ginkgolide B (GB), a specific inhibitor of PAFR, enhanced both CDDP chemosusceptibility and apoptosis. We next evaluated the downstream signaling pathway of PAFR in si<i>PAFR</i>-treated cells and GB-treated cells after CDDP treatment. In both cases, we observed decreased phosphorylation of ERK and Akt and increased expression of cleaved caspase-3. These results suggest that PAFR is a therapeutic target for modulating CDDP sensitivity in OSCC cells. Thus, GB may be a novel drug that could enhance combination chemotherapy with CDDP for OSCC patients. |
| first_indexed | 2024-03-10T04:31:54Z |
| format | Article |
| id | doaj.art-886ab3a2e1a14e7cbc5b6f321c19f9a2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:31:54Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-886ab3a2e1a14e7cbc5b6f321c19f9a22023-11-23T04:06:42ZengMDPI AGCancers2072-66942021-12-011324629910.3390/cancers13246299Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor PathwayKohei Kawasaki0Atsushi Kasamatsu1Toshiaki Ando2Tomoaki Saito3Takafumi Nobuchi4Ryunosuke Nozaki5Manabu Iyoda6Katsuhiro Uzawa7Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, JapanDepartment of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8677, JapanDepartment of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, JapanDepartment of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8677, JapanDepartment of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, JapanDepartment of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, JapanDepartment of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8677, JapanDepartment of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, JapanThe platelet-activating factor receptor (PAFR) is a key molecule that participates in intracellular signaling pathways, including regulating the activation of kinases. It is involved in cancer progression, but the detailed mechanism of its chemosensitivity is unknown. The purpose of the current study was to elucidate the mechanism regulating cisplatin (CDDP) sensitivity through PAFR functions in oral squamous cell carcinoma (OSCC). We first analyzed the correlation between PAFR expression and CDDP sensitivity in seven OSCC-derived cell lines based upon cell viability assays. Among them, we isolated 2 CDDP-resistant cell lines (Ca9-22 and Ho-1-N-1). In addition to conducting PAFR-knockdown (si<i>PAFR</i>) experiments, we found that ginkgolide B (GB), a specific inhibitor of PAFR, enhanced both CDDP chemosusceptibility and apoptosis. We next evaluated the downstream signaling pathway of PAFR in si<i>PAFR</i>-treated cells and GB-treated cells after CDDP treatment. In both cases, we observed decreased phosphorylation of ERK and Akt and increased expression of cleaved caspase-3. These results suggest that PAFR is a therapeutic target for modulating CDDP sensitivity in OSCC cells. Thus, GB may be a novel drug that could enhance combination chemotherapy with CDDP for OSCC patients.https://www.mdpi.com/2072-6694/13/24/6299platelet-activating factor receptorcisplatinginkgolide Boral squamous cell carcinomacombination chemotherapy |
| spellingShingle | Kohei Kawasaki Atsushi Kasamatsu Toshiaki Ando Tomoaki Saito Takafumi Nobuchi Ryunosuke Nozaki Manabu Iyoda Katsuhiro Uzawa Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway Cancers platelet-activating factor receptor cisplatin ginkgolide B oral squamous cell carcinoma combination chemotherapy |
| title | Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway |
| title_full | Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway |
| title_fullStr | Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway |
| title_full_unstemmed | Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway |
| title_short | Ginkgolide B Regulates CDDP Chemoresistance in Oral Cancer via the Platelet-Activating Factor Receptor Pathway |
| title_sort | ginkgolide b regulates cddp chemoresistance in oral cancer via the platelet activating factor receptor pathway |
| topic | platelet-activating factor receptor cisplatin ginkgolide B oral squamous cell carcinoma combination chemotherapy |
| url | https://www.mdpi.com/2072-6694/13/24/6299 |
| work_keys_str_mv | AT koheikawasaki ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway AT atsushikasamatsu ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway AT toshiakiando ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway AT tomoakisaito ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway AT takafuminobuchi ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway AT ryunosukenozaki ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway AT manabuiyoda ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway AT katsuhirouzawa ginkgolidebregulatescddpchemoresistanceinoralcancerviatheplateletactivatingfactorreceptorpathway |