Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal Adenocarcinoma
<i>Background and Objectives</i>: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is involved in pancreatic cancer progression and is an attractive therapeutic target for pancreatic cancer. In this study, we evaluated the therapeutic efficacy of small-interfering RNA...
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2025-03-01
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| author | Hongsik Kim Chang-Gok Woo Seung-Myoung Son Yong-Pyo Lee Hee-Kyung Kim Yaewon Yang Jihyun Kwon Ki-Hyeong Lee Ho-Chang Lee Ok-Jun Lee Hye-Sook Han |
| author_facet | Hongsik Kim Chang-Gok Woo Seung-Myoung Son Yong-Pyo Lee Hee-Kyung Kim Yaewon Yang Jihyun Kwon Ki-Hyeong Lee Ho-Chang Lee Ok-Jun Lee Hye-Sook Han |
| author_sort | Hongsik Kim |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is involved in pancreatic cancer progression and is an attractive therapeutic target for pancreatic cancer. In this study, we evaluated the therapeutic efficacy of small-interfering RNA (siRNA) targeting CEACAM6 (siCEACAM6) and the CEACAM6-suppressive microRNA-29a (miR-29a) in a pancreatic ductal adenocarcinoma xenograft mouse model using pH-low insertion peptide (pHLIP) technology, which targets the acidic tumor microenvironment. <i>Materials and Methods</i>: The delivery vectors for siRNA and miRNA were constructed by conjugating the peptide nucleic acid forms of siCEACAM6 and miR-29a to a peptide with a pHLIP, enabling the transport of siRNA and miRNA across the plasma membrane. The tumor-suppressive effects of pHLIP-siCEACAM6 and pHLIP-miR-29a were assessed in vivo using a BALB/c xenograft mouse model with the injection of the CFPAC-1 human pancreatic ductal adenocarcinoma cell line. <i>Results</i>: The treatment of CFPAC-1 cells with pHLIP-siCEACAM6 and pHLIP-miR-29a under acidic pH conditions suppressed CEACAM6 expression and decreased cell viability. In a xenograft mouse model, the intravenous injection of pHLIP-siCEACAM6 and pHLIP-miR-29a suppressed tumor growth by up to 25.1% (<i>p</i> < 0.01) and 21.2% (<i>p</i> < 0.01), respectively, compared to the control mice treated with pHLIP-scr. <i>Conclusions</i>: Our results demonstrated the efficacy of the pHLIP-mediated delivery of siCEACAM6 and miR-29a as a promising therapeutic strategy in a pancreatic ductal adenocarcinoma xenograft mouse model. The pHLIP technology, which targets the acidic tumor microenvironment, represents an innovative approach to the delivery of small RNAs to pancreatic ductal adenocarcinoma cells, providing new potential strategies for pancreatic cancer treatment. |
| format | Article |
| id | doaj-art-e1bf7877b32d48e985fa6d09dc74092f |
| institution | DOAJ |
| issn | 1010-660X 1648-9144 |
| language | English |
| publishDate | 2025-03-01 |
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| series | Medicina |
| spelling | doaj-art-e1bf7877b32d48e985fa6d09dc74092f2025-08-20T03:13:55ZengMDPI AGMedicina1010-660X1648-91442025-03-0161459810.3390/medicina61040598Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal AdenocarcinomaHongsik Kim0Chang-Gok Woo1Seung-Myoung Son2Yong-Pyo Lee3Hee-Kyung Kim4Yaewon Yang5Jihyun Kwon6Ki-Hyeong Lee7Ho-Chang Lee8Ok-Jun Lee9Hye-Sook Han10Department of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Pathology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Pathology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Pathology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Pathology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Internal Medicine, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea<i>Background and Objectives</i>: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is involved in pancreatic cancer progression and is an attractive therapeutic target for pancreatic cancer. In this study, we evaluated the therapeutic efficacy of small-interfering RNA (siRNA) targeting CEACAM6 (siCEACAM6) and the CEACAM6-suppressive microRNA-29a (miR-29a) in a pancreatic ductal adenocarcinoma xenograft mouse model using pH-low insertion peptide (pHLIP) technology, which targets the acidic tumor microenvironment. <i>Materials and Methods</i>: The delivery vectors for siRNA and miRNA were constructed by conjugating the peptide nucleic acid forms of siCEACAM6 and miR-29a to a peptide with a pHLIP, enabling the transport of siRNA and miRNA across the plasma membrane. The tumor-suppressive effects of pHLIP-siCEACAM6 and pHLIP-miR-29a were assessed in vivo using a BALB/c xenograft mouse model with the injection of the CFPAC-1 human pancreatic ductal adenocarcinoma cell line. <i>Results</i>: The treatment of CFPAC-1 cells with pHLIP-siCEACAM6 and pHLIP-miR-29a under acidic pH conditions suppressed CEACAM6 expression and decreased cell viability. In a xenograft mouse model, the intravenous injection of pHLIP-siCEACAM6 and pHLIP-miR-29a suppressed tumor growth by up to 25.1% (<i>p</i> < 0.01) and 21.2% (<i>p</i> < 0.01), respectively, compared to the control mice treated with pHLIP-scr. <i>Conclusions</i>: Our results demonstrated the efficacy of the pHLIP-mediated delivery of siCEACAM6 and miR-29a as a promising therapeutic strategy in a pancreatic ductal adenocarcinoma xenograft mouse model. The pHLIP technology, which targets the acidic tumor microenvironment, represents an innovative approach to the delivery of small RNAs to pancreatic ductal adenocarcinoma cells, providing new potential strategies for pancreatic cancer treatment.https://www.mdpi.com/1648-9144/61/4/598pancreatic ductal adenocarcinomapHLIPCEACAM6drug deliverytumor acidity |
| spellingShingle | Hongsik Kim Chang-Gok Woo Seung-Myoung Son Yong-Pyo Lee Hee-Kyung Kim Yaewon Yang Jihyun Kwon Ki-Hyeong Lee Ho-Chang Lee Ok-Jun Lee Hye-Sook Han Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal Adenocarcinoma Medicina pancreatic ductal adenocarcinoma pHLIP CEACAM6 drug delivery tumor acidity |
| title | Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal Adenocarcinoma |
| title_full | Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal Adenocarcinoma |
| title_short | Targeted Suppression of CEACAM6 via pHLIP-Delivered RNAs in Pancreatic Ductal Adenocarcinoma |
| title_sort | targeted suppression of ceacam6 via phlip delivered rnas in pancreatic ductal adenocarcinoma |
| topic | pancreatic ductal adenocarcinoma pHLIP CEACAM6 drug delivery tumor acidity |
| url | https://www.mdpi.com/1648-9144/61/4/598 |
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