{"id":62982,"date":"2022-10-24T11:36:34","date_gmt":"2022-10-24T09:36:34","guid":{"rendered":"https:\/\/cri1149.mlcom-dev.net\/?post_type=publications&#038;p=62982"},"modified":"2025-09-11T16:47:59","modified_gmt":"2025-09-11T14:47:59","slug":"the-orexin-a-ox1r-system-induces-cell-death-in-pancreatic-cancer-cells-resistant-to-gemcitabine-and-nab-paclitaxel-treatment","status":"publish","type":"publication","link":"https:\/\/cri1149.mlcom-dev.net\/en\/publication\/the-orexin-a-ox1r-system-induces-cell-death-in-pancreatic-cancer-cells-resistant-to-gemcitabine-and-nab-paclitaxel-treatment\/","title":{"rendered":"The Orexin-A\/OX1R System Induces Cell Death in Pancreatic Cancer Cells Resistant to Gemcitabine and Nab-Paclitaxel Treatment"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"class_list":["post-62982","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"Frontiers on Oncology","date_de_publication":"20220607","numero_doi":"","equipe":[],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13167,"auteur-text":""},{"texte_libre":false,"auteur-lien":13130,"auteur-text":""},{"texte_libre":false,"auteur-lien":13082,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:fr]Ana\u00efs Chassac[:]"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"[:fr]Dounia Mansour[:]"},{"texte_libre":false,"auteur-lien":13146,"auteur-text":""},{"texte_libre":false,"auteur-lien":13054,"auteur-text":""},{"texte_libre":false,"auteur-lien":13053,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.904327\/full"}],"paragraphe":"[:fr]<p style=\"text-align: justify;\">Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-associated death in the West. This type of cancer has a very poor prognosis notably due to the development of chemoresistance when treatments including gemcitabine and Abraxane (Nab-paclitaxel) were prescribed. The identification of new treatment circumventing this chemoresistance represents a key challenge. Previous studies demonstrated that the activation of orexin receptor type 1 (OX1R), which was ectopically expressed in PDAC, by its natural ligand named orexin-A (OxA), led to anti-tumoral effect resulting in the activation of mitochondrial pro-apoptotic mechanism. Here, we demonstrated that OxA inhibited the pancreatic cancer cell (AsPC-1) growth and inhibited the tumor volume in preclinical models as effectively as gemcitabine and Nab-paclitaxel. Moreover, the combination therapy including OxA plus gemcitabine or OxA plus Nab-paclitaxel was additive on the inhibition of cancer cell growth and tumor development. More importantly, the treatment by OxA of chemoresistant tumors to gemcitabine or Nab-paclitaxel obtained by successive xenografts in mice revealed that OxA was able to induce a strong inhibition of tumor development, whereas no OxA resistance was identified in tumors. The OX1R\/OxA system might be an innovative and powerful alternative treatment of chemoresistant PDAC.<\/p>\r\n<p>&nbsp;<\/p>\r\n<p><img class=\" wp-image-62983 aligncenter\" src=\"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2022\/10\/couvineau-onco-2022-300x198.jpg\" alt=\"\" width=\"863\" height=\"569\" \/><\/p>\r\n<p style=\"text-align: justify;\"><strong>Preclinical study and histological analysis of anti-tumoral effect of OxA and Nab-paclitaxel.<\/strong>\u00a0<strong>(A)<\/strong>\u00a0Impact of three injections\/week of 100 \u00b5g OxA, 230 \u00b5g Nab-paclitaxel, or 100 \u00b5g OxA plus 230 \u00b5g Nab-paclitaxel on volume of tumors developed from subcutaneously xenografted ASPC-1 cells in nude mice. The tumor development was measured with a caliper.\u00a0<strong>(B)<\/strong>\u00a0Determination of OX1R expression and caspase-3 activation by histologic immunostaining in xenografted AsPC-1 resected tumors from mice treated with PBS (control), OxA (OxA), Nab-paclitaxel (pacli), or OxA plus Nab-paclitaxel (OxA + pacli). Magnification was 40\u00d7 (OX1R expression) and 20\u00d7 (caspase-3 activation). Data were the means \u00b1 SEM of six tumors in each group. *p&lt;0.05.<\/p>\r\n<p>&nbsp;<\/p>[:]","paragraphe_en":"[:fr]<p style=\"text-align: justify;\">Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-associated death in the West. This type of cancer has a very poor prognosis notably due to the development of chemoresistance when treatments including gemcitabine and Abraxane (Nab-paclitaxel) were prescribed. The identification of new treatment circumventing this chemoresistance represents a key challenge. Previous studies demonstrated that the activation of orexin receptor type 1 (OX1R), which was ectopically expressed in PDAC, by its natural ligand named orexin-A (OxA), led to anti-tumoral effect resulting in the activation of mitochondrial pro-apoptotic mechanism. Here, we demonstrated that OxA inhibited the pancreatic cancer cell (AsPC-1) growth and inhibited the tumor volume in preclinical models as effectively as gemcitabine and Nab-paclitaxel. Moreover, the combination therapy including OxA plus gemcitabine or OxA plus Nab-paclitaxel was additive on the inhibition of cancer cell growth and tumor development. More importantly, the treatment by OxA of chemoresistant tumors to gemcitabine or Nab-paclitaxel obtained by successive xenografts in mice revealed that OxA was able to induce a strong inhibition of tumor development, whereas no OxA resistance was identified in tumors. The OX1R\/OxA system might be an innovative and powerful alternative treatment of chemoresistant PDAC.<\/p>\r\n<p>&nbsp;<\/p>\r\n<p><img class=\" wp-image-62983 aligncenter\" src=\"https:\/\/cri1149.mlcom-dev.net\/wp-content\/uploads\/2022\/10\/couvineau-onco-2022-300x198.jpg\" alt=\"\" width=\"863\" height=\"569\" \/><\/p>\r\n<p style=\"text-align: justify;\"><strong>Preclinical study and histological analysis of anti-tumoral effect of OxA and Nab-paclitaxel.<\/strong>\u00a0<strong>(A)<\/strong>\u00a0Impact of three injections\/week of 100 \u00b5g OxA, 230 \u00b5g Nab-paclitaxel, or 100 \u00b5g OxA plus 230 \u00b5g Nab-paclitaxel on volume of tumors developed from subcutaneously xenografted ASPC-1 cells in nude mice. The tumor development was measured with a caliper.\u00a0<strong>(B)<\/strong>\u00a0Determination of OX1R expression and caspase-3 activation by histologic immunostaining in xenografted AsPC-1 resected tumors from mice treated with PBS (control), OxA (OxA), Nab-paclitaxel (pacli), or OxA plus Nab-paclitaxel (OxA + pacli). Magnification was 40\u00d7 (OX1R expression) and 20\u00d7 (caspase-3 activation). Data were the means \u00b1 SEM of six tumors in each group. *p&lt;0.05.<\/p>\r\n<p>&nbsp;<\/p>[:]","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>The Orexin-A\/OX1R System Induces Cell Death in Pancreatic Cancer Cells Resistant to Gemcitabine and Nab-Paclitaxel Treatment - CRI<\/title>\n<meta name=\"robots\" content=\"noindex, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Orexin-A\/OX1R System Induces Cell Death in Pancreatic Cancer Cells Resistant to Gemcitabine and Nab-Paclitaxel Treatment - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.mlcom-dev.net\/publication\/the-orexin-a-ox1r-system-induces-cell-death-in-pancreatic-cancer-cells-resistant-to-gemcitabine-and-nab-paclitaxel-treatment\/\" \/>\n<meta property=\"og:site_name\" content=\"CRI\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\" \/>\n<meta property=\"article:modified_time\" content=\"2025-09-11T14:47:59+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/the-orexin-a-ox1r-system-induces-cell-death-in-pancreatic-cancer-cells-resistant-to-gemcitabine-and-nab-paclitaxel-treatment\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/the-orexin-a-ox1r-system-induces-cell-death-in-pancreatic-cancer-cells-resistant-to-gemcitabine-and-nab-paclitaxel-treatment\/\",\"name\":\"The Orexin-A\/OX1R System Induces Cell Death in Pancreatic Cancer Cells Resistant to Gemcitabine and Nab-Paclitaxel Treatment - 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