The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine

Abstract Pancreatic cancer is one of the most lethal and chemo-resistant cancers worldwide. Growing evidence supports the theory that the gut microbiota plays an essential role in modulating the host response to anti-cancer therapy. The present study aimed to explore the effect of probiotics as an a...

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Autores principales:	Shan-Ming Chen, Wee-Wei Chieng, Szu-Wei Huang, Li-Jin Hsu, Ming-Shiou Jan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15cf03039bce4227a77ea1f341924212
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spelling	oai:doaj.org-article:15cf03039bce4227a77ea1f3419242122021-12-02T15:09:23ZThe synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine10.1038/s41598-020-77322-52045-2322https://doaj.org/article/15cf03039bce4227a77ea1f3419242122020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77322-5https://doaj.org/toc/2045-2322Abstract Pancreatic cancer is one of the most lethal and chemo-resistant cancers worldwide. Growing evidence supports the theory that the gut microbiota plays an essential role in modulating the host response to anti-cancer therapy. The present study aimed to explore the effect of probiotics as an adjuvant during chemotherapy for pancreatic cancer. An LSL-Kras G12D/− -Pdx-1-Cre mouse model of pancreatic ductal adenocarcinoma (PDAC) was created to study the effects of using four-week multi-strain probiotics (Lactobacillus paracasei GMNL-133 and Lactobacillus reuteri GMNL-89) as an adjuvant therapy for controlling cancer progression. At 12 weeks of age, pancreatitis was induced in the mice by two intraperitoneal injection with caerulein (25 μg/kg 2 days apart). Over the next 4 weeks the mice were treated with intraperitoneal injections of gemcitabine in combination with the oral administration of probiotics. The pancreas was then harvested for analysis. Following caerulein treatment, the pancreases of the LSL-Kras G12D/− -Pdx-1-Cre transgenic mice exhibited more extensive pancreatic intraepithelial neoplasia (PanIN) formation. Combined treatment with gemcitabine and probiotics revealed a lower grade of PanIN formation and a decrease in the expression of vimentin and Ki-67. Mice that received gemcitabine in combination with probiotics had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Notably, the use of high-dose probiotics alone without gemcitabine also had an inhibitory effect on PanIN changes and serum liver enzyme elevation. These findings suggest that probiotics are able to make standard chemotherapy more effective and could help improve the patient’s tolerance of chemotherapy.Shan-Ming ChenWee-Wei ChiengSzu-Wei HuangLi-Jin HsuMing-Shiou JanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shan-Ming Chen Wee-Wei Chieng Szu-Wei Huang Li-Jin Hsu Ming-Shiou Jan The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine
description	Abstract Pancreatic cancer is one of the most lethal and chemo-resistant cancers worldwide. Growing evidence supports the theory that the gut microbiota plays an essential role in modulating the host response to anti-cancer therapy. The present study aimed to explore the effect of probiotics as an adjuvant during chemotherapy for pancreatic cancer. An LSL-Kras G12D/− -Pdx-1-Cre mouse model of pancreatic ductal adenocarcinoma (PDAC) was created to study the effects of using four-week multi-strain probiotics (Lactobacillus paracasei GMNL-133 and Lactobacillus reuteri GMNL-89) as an adjuvant therapy for controlling cancer progression. At 12 weeks of age, pancreatitis was induced in the mice by two intraperitoneal injection with caerulein (25 μg/kg 2 days apart). Over the next 4 weeks the mice were treated with intraperitoneal injections of gemcitabine in combination with the oral administration of probiotics. The pancreas was then harvested for analysis. Following caerulein treatment, the pancreases of the LSL-Kras G12D/− -Pdx-1-Cre transgenic mice exhibited more extensive pancreatic intraepithelial neoplasia (PanIN) formation. Combined treatment with gemcitabine and probiotics revealed a lower grade of PanIN formation and a decrease in the expression of vimentin and Ki-67. Mice that received gemcitabine in combination with probiotics had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Notably, the use of high-dose probiotics alone without gemcitabine also had an inhibitory effect on PanIN changes and serum liver enzyme elevation. These findings suggest that probiotics are able to make standard chemotherapy more effective and could help improve the patient’s tolerance of chemotherapy.
format	article
author	Shan-Ming Chen Wee-Wei Chieng Szu-Wei Huang Li-Jin Hsu Ming-Shiou Jan
author_facet	Shan-Ming Chen Wee-Wei Chieng Szu-Wei Huang Li-Jin Hsu Ming-Shiou Jan
author_sort	Shan-Ming Chen
title	The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine
title_short	The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine
title_full	The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine
title_fullStr	The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine
title_full_unstemmed	The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine
title_sort	synergistic tumor growth-inhibitory effect of probiotic lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/15cf03039bce4227a77ea1f341924212
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The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine

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