CLT-003 exerts anti-tumor activity in pancreatic cancer by blocking the PI3K/AKT/HIF-1α pathway Article Swipe
Chao Xu
,
Zekun Li
,
Yu Shan
,
Chunhua She
,
Yanfang Yang
,
Tao Zhou
,
Yongjie Xie
,
Bo Ni
,
Chenyang Meng
,
Guangcong Shen
,
Boyang Fu
,
Guannan Sheng
,
Liangliang Wu
,
Jingjing Pei
,
Tiansuo Zhao
,
Song Gao
,
Hongwei Wang
,
Chengqi Deng
,
Kaiyuan Wang
,
Antao Chang
,
Chongbiao Huang
,
Lei Shi
,
Shengyu Yang
,
Jun Yu
,
Jin Hao
,
Xiuchao Wang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.20892/j.issn.2095-3941.2025.0058
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.20892/j.issn.2095-3941.2025.0058
Objective: CLT-003 is a novel phenylphthalimide derivative encapsulated in poly (lactate-glycolic acid) copolymer nanoparticles using nanotechnology techniques. CLT-003 possesses anti-angiogenetic and antitumor activities. Nevertheless, the role and molecular mechanism underlying CLT-003 in pancreatic cancer remain to be elucidated. Methods: Cell proliferation and apoptosis were detected using CCK-8, real-time cell analysis (RTCA), EdU, and flow cytometric assays. Cellular mobility and invasive capacity were detected using wound-healing, Transwell, and cell motility assays. Tumor growth and metastasis were determined using the mouse subcutaneous and pancreatic cancer orthotopic liver metastasis models. The antitumor effects of CLT-003 were evaluated using patient-derived organoid (PDO) and patient-derived xenograft (PDX) models. Results: CLT-003 significantly inhibited cellular proliferation, enhanced cellular apoptosis, and attenuated cellular invasion and migration of pancreatic cancer cells. Mechanistically, CLT-003 suppressed the translation of HIF-1α by inhibiting the PI3K/AKT/mTOR signaling pathway. In the mouse tumor models, CLT-003 significantly inhibited the growth and metastasis of pancreatic tumors. Moreover, the PDO and PDX models showed increased sensitivity to CLT-003 in pancreatic cancer with high HIF-1α expression compared to pancreatic cancer with low HIF-1α expression. Conclusions: This study delineated the role and molecular mechanism of CLT-003 action in impeding the progression of pancreatic cancer and indicated its robust potential for the treatment of pancreatic cancer.
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- article
- Language
- en
- Landing Page
- https://doi.org/10.20892/j.issn.2095-3941.2025.0058
- OA Status
- gold
- OpenAlex ID
- https://openalex.org/W4414669394
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- OpenAlex ID
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https://openalex.org/W4414669394Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.20892/j.issn.2095-3941.2025.0058Digital Object Identifier
- Title
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CLT-003 exerts anti-tumor activity in pancreatic cancer by blocking the PI3K/AKT/HIF-1α pathwayWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-09-30Full publication date if available
- Authors
-
Chao Xu, Zekun Li, Yu Shan, Chunhua She, Yanfang Yang, Tao Zhou, Yongjie Xie, Bo Ni, Chenyang Meng, Guangcong Shen, Boyang Fu, Guannan Sheng, Liangliang Wu, Jingjing Pei, Tiansuo Zhao, Song Gao, Hongwei Wang, Chengqi Deng, Kaiyuan Wang, Antao Chang, Chongbiao Huang, Lei Shi, Shengyu Yang, Jun Yu, Jin Hao, Xiuchao WangList of authors in order
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https://doi.org/10.20892/j.issn.2095-3941.2025.0058Publisher landing page
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://doi.org/10.20892/j.issn.2095-3941.2025.0058Direct OA link when available
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| abstract_inverted_index.by | 129 |
| abstract_inverted_index.in | 8, 31, 161, 188 |
| abstract_inverted_index.is | 2 |
| abstract_inverted_index.of | 90, 118, 127, 147, 185, 192, 203 |
| abstract_inverted_index.to | 35, 159, 169 |
| abstract_inverted_index.PDO | 152 |
| abstract_inverted_index.PDX | 154 |
| abstract_inverted_index.The | 87 |
| abstract_inverted_index.and | 20, 26, 41, 52, 58, 66, 72, 80, 98, 112, 116, 145, 153, 182, 195 |
| abstract_inverted_index.for | 200 |
| abstract_inverted_index.its | 197 |
| abstract_inverted_index.low | 173 |
| abstract_inverted_index.the | 24, 77, 125, 131, 136, 143, 151, 180, 190, 201 |
| abstract_inverted_index.Cell | 39 |
| abstract_inverted_index.EdU, | 51 |
| abstract_inverted_index.This | 177 |
| abstract_inverted_index.cell | 48, 67 |
| abstract_inverted_index.flow | 53 |
| abstract_inverted_index.high | 165 |
| abstract_inverted_index.poly | 9 |
| abstract_inverted_index.role | 25, 181 |
| abstract_inverted_index.were | 43, 61, 74, 92 |
| abstract_inverted_index.with | 164, 172 |
| abstract_inverted_index.(PDO) | 97 |
| abstract_inverted_index.(PDX) | 101 |
| abstract_inverted_index.Tumor | 70 |
| abstract_inverted_index.acid) | 11 |
| abstract_inverted_index.liver | 84 |
| abstract_inverted_index.mouse | 78, 137 |
| abstract_inverted_index.novel | 4 |
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| abstract_inverted_index.tumor | 138 |
| abstract_inverted_index.using | 14, 45, 63, 76, 94 |
| abstract_inverted_index.CCK-8, | 46 |
| abstract_inverted_index.action | 187 |
| abstract_inverted_index.cancer | 33, 82, 120, 163, 171, 194 |
| abstract_inverted_index.cells. | 121 |
| abstract_inverted_index.growth | 71, 144 |
| abstract_inverted_index.models | 155 |
| abstract_inverted_index.remain | 34 |
| abstract_inverted_index.robust | 198 |
| abstract_inverted_index.showed | 156 |
| abstract_inverted_index.(RTCA), | 50 |
| abstract_inverted_index.CLT-003 | 1, 17, 30, 91, 104, 123, 140, 160, 186 |
| abstract_inverted_index.assays. | 55, 69 |
| abstract_inverted_index.cancer. | 205 |
| abstract_inverted_index.effects | 89 |
| abstract_inverted_index.models, | 139 |
| abstract_inverted_index.models. | 86, 102 |
| abstract_inverted_index.tumors. | 149 |
| abstract_inverted_index.Cellular | 56 |
| abstract_inverted_index.Methods: | 38 |
| abstract_inverted_index.Results: | 103 |
| abstract_inverted_index.analysis | 49 |
| abstract_inverted_index.capacity | 60 |
| abstract_inverted_index.cellular | 107, 110, 114 |
| abstract_inverted_index.compared | 168 |
| abstract_inverted_index.detected | 44, 62 |
| abstract_inverted_index.enhanced | 109 |
| abstract_inverted_index.impeding | 189 |
| abstract_inverted_index.invasion | 115 |
| abstract_inverted_index.invasive | 59 |
| abstract_inverted_index.mobility | 57 |
| abstract_inverted_index.motility | 68 |
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| abstract_inverted_index.pathway. | 134 |
| abstract_inverted_index.Moreover, | 150 |
| abstract_inverted_index.antitumor | 21, 88 |
| abstract_inverted_index.apoptosis | 42 |
| abstract_inverted_index.copolymer | 12 |
| abstract_inverted_index.evaluated | 93 |
| abstract_inverted_index.increased | 157 |
| abstract_inverted_index.indicated | 196 |
| abstract_inverted_index.inhibited | 106, 142 |
| abstract_inverted_index.mechanism | 28, 184 |
| abstract_inverted_index.migration | 117 |
| abstract_inverted_index.molecular | 27, 183 |
| abstract_inverted_index.possesses | 18 |
| abstract_inverted_index.potential | 199 |
| abstract_inverted_index.real-time | 47 |
| abstract_inverted_index.signaling | 133 |
| abstract_inverted_index.treatment | 202 |
| abstract_inverted_index.xenograft | 100 |
| abstract_inverted_index.Objective: | 0 |
| abstract_inverted_index.Transwell, | 65 |
| abstract_inverted_index.apoptosis, | 111 |
| abstract_inverted_index.attenuated | 113 |
| abstract_inverted_index.cytometric | 54 |
| abstract_inverted_index.delineated | 179 |
| abstract_inverted_index.derivative | 6 |
| abstract_inverted_index.determined | 75 |
| abstract_inverted_index.expression | 167 |
| abstract_inverted_index.inhibiting | 130 |
| abstract_inverted_index.metastasis | 73, 85, 146 |
| abstract_inverted_index.orthotopic | 83 |
| abstract_inverted_index.pancreatic | 32, 81, 119, 148, 162, 170, 193, 204 |
| abstract_inverted_index.suppressed | 124 |
| abstract_inverted_index.underlying | 29 |
| abstract_inverted_index.activities. | 22 |
| abstract_inverted_index.elucidated. | 37 |
| abstract_inverted_index.expression. | 175 |
| abstract_inverted_index.progression | 191 |
| abstract_inverted_index.sensitivity | 158 |
| abstract_inverted_index.techniques. | 16 |
| abstract_inverted_index.translation | 126 |
| abstract_inverted_index.Conclusions: | 176 |
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| abstract_inverted_index.subcutaneous | 79 |
| abstract_inverted_index.Nevertheless, | 23 |
| abstract_inverted_index.PI3K/AKT/mTOR | 132 |
| abstract_inverted_index.nanoparticles | 13 |
| abstract_inverted_index.proliferation | 40 |
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| abstract_inverted_index.nanotechnology | 15 |
| abstract_inverted_index.proliferation, | 108 |
| abstract_inverted_index.wound-healing, | 64 |
| abstract_inverted_index.patient-derived | 95, 99 |
| abstract_inverted_index.Mechanistically, | 122 |
| abstract_inverted_index.(lactate-glycolic | 10 |
| abstract_inverted_index.HIF-1α | 128, 166, 174 |
| abstract_inverted_index.anti-angiogenetic | 19 |
| abstract_inverted_index.phenylphthalimide | 5 |
| cited_by_percentile_year | |
| countries_distinct_count | 2 |
| institutions_distinct_count | 26 |
| citation_normalized_percentile.value | 0.50047324 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |