Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma
Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer. To i...
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| Veröffentlicht in: | Cancers 2022-05, Vol.14 (10), p.2395 |
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| creator | Matsumura, Shinya Ishikawa, Takeshi Yoshida, Juichiro Morita, Ryuichi Sakakida, Tomoki Endo, Yuki Doi, Toshifumi Hirose, Ryohei Inoue, Ken Dohi, Osamu Yoshida, Naohisa Uchiyama, Kazuhiko Takagi, Tomohisa Konishi, Hideyuki Yasui, Kohichiroh Naito, Yuji Itoh, Yoshito |
| description | Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer.
To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017.
In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (
= 0.009, HR, 0.33; 95% CI, 0.12-0.76).
PPI treatment may safely enhance chemosensitivity in esophageal cancer patients. |
| doi_str_mv | 10.3390/cancers14102395 |
| format | Article |
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To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017.
In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (
= 0.009, HR, 0.33; 95% CI, 0.12-0.76).
PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers14102395</identifier><identifier>PMID: 35626000</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>5-Fluorouracil ; Acidosis ; Adenosine triphosphatase ; Antitumor activity ; Cancer therapies ; Cell viability ; Chemotherapy ; Cytotoxicity ; Esophageal cancer ; Esophagus ; H+-transporting ATPase ; Laboratories ; Medical research ; Membranes ; Metastasis ; Multivariate analysis ; Omeprazole ; Patients ; Proteins ; Proton pump inhibitors ; Squamous cell carcinoma ; Tumor cell lines ; Tumors ; Ulcers</subject><ispartof>Cancers, 2022-05, Vol.14 (10), p.2395</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c542t-59681d8e584b3a0bd4d6940eee884c18139f84e8c2250c7a6d57413ce655d073</citedby><cites>FETCH-LOGICAL-c542t-59681d8e584b3a0bd4d6940eee884c18139f84e8c2250c7a6d57413ce655d073</cites><orcidid>0000-0003-0403-8826 ; 0000-0001-9890-3635 ; 0000-0002-0498-0144 ; 0000-0002-5770-9710 ; 0000-0002-6119-4828 ; 0000-0001-5443-788X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140098/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9140098/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35626000$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsumura, Shinya</creatorcontrib><creatorcontrib>Ishikawa, Takeshi</creatorcontrib><creatorcontrib>Yoshida, Juichiro</creatorcontrib><creatorcontrib>Morita, Ryuichi</creatorcontrib><creatorcontrib>Sakakida, Tomoki</creatorcontrib><creatorcontrib>Endo, Yuki</creatorcontrib><creatorcontrib>Doi, Toshifumi</creatorcontrib><creatorcontrib>Hirose, Ryohei</creatorcontrib><creatorcontrib>Inoue, Ken</creatorcontrib><creatorcontrib>Dohi, Osamu</creatorcontrib><creatorcontrib>Yoshida, Naohisa</creatorcontrib><creatorcontrib>Uchiyama, Kazuhiko</creatorcontrib><creatorcontrib>Takagi, Tomohisa</creatorcontrib><creatorcontrib>Konishi, Hideyuki</creatorcontrib><creatorcontrib>Yasui, Kohichiroh</creatorcontrib><creatorcontrib>Naito, Yuji</creatorcontrib><creatorcontrib>Itoh, Yoshito</creatorcontrib><title>Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer.
To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017.
In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (
= 0.009, HR, 0.33; 95% CI, 0.12-0.76).
PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.</description><subject>5-Fluorouracil</subject><subject>Acidosis</subject><subject>Adenosine triphosphatase</subject><subject>Antitumor activity</subject><subject>Cancer therapies</subject><subject>Cell viability</subject><subject>Chemotherapy</subject><subject>Cytotoxicity</subject><subject>Esophageal cancer</subject><subject>Esophagus</subject><subject>H+-transporting ATPase</subject><subject>Laboratories</subject><subject>Medical research</subject><subject>Membranes</subject><subject>Metastasis</subject><subject>Multivariate analysis</subject><subject>Omeprazole</subject><subject>Patients</subject><subject>Proteins</subject><subject>Proton pump inhibitors</subject><subject>Squamous cell carcinoma</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Ulcers</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1rFTEUxYMottSu3UnAjZtn853MRijDUwsFC3Yf8jJ3OvOYSaZJRuh_b4bWUpvNDTm_e8jhIPSRkq-cN-TCu-AhZSooYbyRb9ApI5rtlGrE2xf3E3Se85HUwznVSr9HJ1wqpurDKTrepFhiwDfrvOCrMIyHscSU8T4MmzsuA-DLUMayzjHhfd-DLzj2uB1gjlVMbnnA_SbluAzuDtyEf9-vbo5rxi1ME25d8mOIs_uA3vVuynD-NM_Q7ff9bftzd_3rx1V7eb3zUrCyk40ytDMgjThwRw6d6GoIAgDGCE8N5U1vBBjPmCReO9VJLSj3oKTsiOZn6Nuj7bIeZug8hJLcZJc0zi492OhG-78SxsHexT-2oYKQxlSDL08GKd6vkIudx-xrFBegprJMaco0Z2xDP79Cj3FNoabbqOqma1GVunikfIo5J-ifP0OJ3Zq0r5qsG59eZnjm__XG_wLUE5uG</recordid><startdate>20220512</startdate><enddate>20220512</enddate><creator>Matsumura, Shinya</creator><creator>Ishikawa, Takeshi</creator><creator>Yoshida, Juichiro</creator><creator>Morita, Ryuichi</creator><creator>Sakakida, Tomoki</creator><creator>Endo, Yuki</creator><creator>Doi, Toshifumi</creator><creator>Hirose, Ryohei</creator><creator>Inoue, Ken</creator><creator>Dohi, Osamu</creator><creator>Yoshida, Naohisa</creator><creator>Uchiyama, Kazuhiko</creator><creator>Takagi, Tomohisa</creator><creator>Konishi, Hideyuki</creator><creator>Yasui, Kohichiroh</creator><creator>Naito, Yuji</creator><creator>Itoh, Yoshito</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0403-8826</orcidid><orcidid>https://orcid.org/0000-0001-9890-3635</orcidid><orcidid>https://orcid.org/0000-0002-0498-0144</orcidid><orcidid>https://orcid.org/0000-0002-5770-9710</orcidid><orcidid>https://orcid.org/0000-0002-6119-4828</orcidid><orcidid>https://orcid.org/0000-0001-5443-788X</orcidid></search><sort><creationdate>20220512</creationdate><title>Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma</title><author>Matsumura, Shinya ; 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The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer.
To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017.
In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (
= 0.009, HR, 0.33; 95% CI, 0.12-0.76).
PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35626000</pmid><doi>10.3390/cancers14102395</doi><orcidid>https://orcid.org/0000-0003-0403-8826</orcidid><orcidid>https://orcid.org/0000-0001-9890-3635</orcidid><orcidid>https://orcid.org/0000-0002-0498-0144</orcidid><orcidid>https://orcid.org/0000-0002-5770-9710</orcidid><orcidid>https://orcid.org/0000-0002-6119-4828</orcidid><orcidid>https://orcid.org/0000-0001-5443-788X</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancers, 2022-05, Vol.14 (10), p.2395 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | 5-Fluorouracil Acidosis Adenosine triphosphatase Antitumor activity Cancer therapies Cell viability Chemotherapy Cytotoxicity Esophageal cancer Esophagus H+-transporting ATPase Laboratories Medical research Membranes Metastasis Multivariate analysis Omeprazole Patients Proteins Proton pump inhibitors Squamous cell carcinoma Tumor cell lines Tumors Ulcers |
| title | Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma |
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