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      KCI등재 SCIE SCOPUS

      20 (S)-ginsenoside Rh2 inhibits colorectal cancer cell growth by suppressing the Axl signaling pathway in vitro and in vivo

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      https://www.riss.kr/link?id=A108124111

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      다국어 초록 (Multilingual Abstract)

      Colorectal cancer (CRC) has a high morbidity and mortality worldwide. 20 (S)-ginsenosideRh2 (G-Rh2) is a natural compound extracted from ginseng, which exhibits anticancer effects in manycancer types. In this study, we demonstrated the effect and unde...

      Colorectal cancer (CRC) has a high morbidity and mortality worldwide. 20 (S)-ginsenosideRh2 (G-Rh2) is a natural compound extracted from ginseng, which exhibits anticancer effects in manycancer types. In this study, we demonstrated the effect and underlying molecular mechanism of G-Rh2 inCRC cells in vitro and in vivo.
      Methods: Cell proliferation, migration, invasion, apoptosis, cell cycle, and western blot assays wereperformed to evaluate the effect of G-Rh2 on CRC cells. In vitro pull-down assay was used to verify theinteraction between G-Rh2 and Axl. Transfection and infection experiments were used to explore thefunction of Axl in CRC cells. CRC xenograft models were used to further investigate the effect of Axlknockdown and G-Rh2 on tumor growth in vivo.
      Results: G-Rh2 significantly inhibited proliferation, migration, and invasion, and induced apoptosis andG0/G1 phase cell cycle arrest in CRC cell lines. G-Rh2 directly binds to Axl and inhibits the Axl signalingpathway in CRC cells. Knockdown of Axl suppressed the growth, migration and invasion ability of CRCcells in vitro and xenograft tumor growth in vivo, whereas overexpression of Axl promoted the growth,migration, and invasion ability of CRC cells. Moreover, G-Rh2 significantly suppressed CRC xenografttumor growth by inhibiting Axl signaling with no obvious toxicity to nude mice.
      Conclusion: Our results indicate that G-Rh2 exerts anticancer activity in vitro and in vivo by suppressingthe Axl signaling pathway. G-Rh2 is a promising candidate for CRC prevention and treatment.

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      참고문헌 (Reference)

      1 Vuoriluoto K, "Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer" 30 : 1436-1448, 2011

      2 Baumann C, "Torka GAS6-expressing and self-sustaining cancer cells in 3D spheroids activate the PDK-RSK-mTOR pathway for survival and drug resistance" 11 : 1430-1447, 2017

      3 Creighton CJ, "The role of epithelial-mesenchymal transition programming in invasion and metastasis : a clinical perspective" 5 : 187-195, 2013

      4 Liu GW, "The reversal effect of ginsenoside Rh2 on drug resistance in human colorectal carcinoma cells and its mechanism" 31 : 189-198, 2018

      5 Uribe DJ, "The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer" 12 : e0179979-, 2017

      6 Goyette MA, "The receptor tyrosine kinase AXL is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression" 23 : 1476-1490, 2018

      7 Rankin EB, "The receptor tyrosine kinase AXL in cancer progression" 8 : 103-, 2016

      8 Li J, "The crosstalk between AXL and YAP promotes tumor progression through STAT3 activation in head and neck squamous cell carcinoma" 111 : 3222-3235, 2020

      9 Akbari Dilmaghani N, "The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma : possibilities for therapeutic interventions either as single agents or in combination with conventional therapies" 73 : 618-642, 2021

      10 Melaragno MG, "The Gas6/Axl system : a novel regulator of vascular cell function" 9 : 250-253, 1999

      1 Vuoriluoto K, "Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer" 30 : 1436-1448, 2011

      2 Baumann C, "Torka GAS6-expressing and self-sustaining cancer cells in 3D spheroids activate the PDK-RSK-mTOR pathway for survival and drug resistance" 11 : 1430-1447, 2017

      3 Creighton CJ, "The role of epithelial-mesenchymal transition programming in invasion and metastasis : a clinical perspective" 5 : 187-195, 2013

      4 Liu GW, "The reversal effect of ginsenoside Rh2 on drug resistance in human colorectal carcinoma cells and its mechanism" 31 : 189-198, 2018

      5 Uribe DJ, "The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer" 12 : e0179979-, 2017

      6 Goyette MA, "The receptor tyrosine kinase AXL is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression" 23 : 1476-1490, 2018

      7 Rankin EB, "The receptor tyrosine kinase AXL in cancer progression" 8 : 103-, 2016

      8 Li J, "The crosstalk between AXL and YAP promotes tumor progression through STAT3 activation in head and neck squamous cell carcinoma" 111 : 3222-3235, 2020

      9 Akbari Dilmaghani N, "The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma : possibilities for therapeutic interventions either as single agents or in combination with conventional therapies" 73 : 618-642, 2021

      10 Melaragno MG, "The Gas6/Axl system : a novel regulator of vascular cell function" 9 : 250-253, 1999

      11 Nunnery SE, "Targeting the PI3K/AKT/mTOR pathway in hormonepositive breast cancer" 80 : 1685-1697, 2020

      12 Liu X, "Targeted therapy of the AKT kinase inhibits esophageal squamous cell carcinoma growth in vitro and in vivo" 145 : 1007-1019, 2019

      13 Lei J, "Src kinase integrates PI3K/Akt and MAPK/ERK1/2 pathways in T3-induced Na-K-ATPase activity in adult rat alveolar cells" 301 : L765-L771, 2011

      14 Ludwig KF, "Small-molecule inhibition of Axl targets tumor immune suppression and enhances chemotherapy in pancreatic cancer" 78 : 246-255, 2018

      15 Ma J, "Reversal effect of ginsenoside Rh2 on oxaliplatin-resistant colon cancer cells and its mechanism" 18 : 630-636, 2019

      16 De Craene B, "Regulatory networks defining EMT during cancer initiation and progression" 13 : 97-110, 2013

      17 Kong L, "Qigesan inhibits esophageal cancer cell invasion and migration by inhibiting Gas6/Axl-induced epithelialmesenchymal transition" 12 : 9714-9725, 2020

      18 Liu H, "PTP1B promotes cell proliferation and metastasis through activating src and ERK1/2 in non-small cell lung cancer" 359 : 218-225, 2015

      19 Miricescu D, "PI3K/AKT/mTOR signaling pathway in breast cancer : from molecular landscape to clinical aspects" 22 : 173-, 2020

      20 Okura N, "ONO-7475, a novel AXL inhibitor, suppresses the adaptive resistance to initial EGFR-TKI treatment in EGFR-mutated non-small lung cancer" 26 : 2244-2256, 2020

      21 Li Y, "Natural compound oblongifolin C confers gemcitabine resistance in pancreatic cancer by downregulating Src/MAPK/ERK pathways" 9 : 538-, 2018

      22 Krishnamoorthy GP, "Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin(17-AAG)-induced AXL receptor tyrosine kinase degradation" 288 : 17481-17494, 2013

      23 Han Y, "MLH1deficiency induces cetuximab resistance in colon cancer via Her-2/PI3K/AKT signaling" 7 : 2000112-, 2020

      24 Chang F, "Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation : a target for cancer chemotherapy" 17 : 590-603, 2003

      25 Bae CA, "Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma" 23 : 824-836, 2020

      26 Tong-Lin Wu T, "Induction of apoptosis in prostate cancer by ginsenoside Rh2" 9 : 11109-11118, 2018

      27 Song X, "Hematopoietic progenitor kinase 1 downregulates the oncogenic receptor tyrosine kinase AXL in pancreatic cancer" 295 : 2348-2358, 2020

      28 Kim HIe, "Growth-stimulatory activity of TIMP-2 is mediated through c-Src activation followed by activation of FAK, PI3-kinase/AKT, and ERK1/2 independent of MMP inhibition in lung adenocarcinoma cells" 6 : 42905-42922, 2015

      29 Jianjun Yang ; Donghong Yuan ; Tongchao Xing ; Hongli Su ; Shengjun Zhang ; Jiansheng Wen ; Qiqiang Bai ; Dongmei Dang, "Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase" 고려인삼학회 40 (40): 400-408, 2016

      30 Ge G, "Ginsenoside Rh2 inhibited proliferation by inducing ROS Mediated ER stress dependent apoptosis in Lung cancer cells" 40 : 2117-2124, 2017

      31 Li B, "Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53" 301 : 185-192, 2011

      32 Li C, "Ginsenoside Rh2 impedes proliferation and migration and induces apoptosis by regulating NF-kappaB, MAPK, and PI3K/Akt/mTOR signaling pathways in osteosarcoma cells" 34 : e22597-, 2020

      33 Hyunkyung Lee ; Seungyeon Lee ; Dawoon Jeong ; Sun Jung Kim, "Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer cells" 고려인삼학회 42 (42): 455-462, 2018

      34 Lv DL, "Ginsenoside GRh2synergizes with SMI-4a in anti-melanoma activity through autophagic cell death" 13 : 11-, 2018

      35 Shi X, "Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through the Akt/GSK3beta signaling pathway in human cervical cancer cells" 17 : 4811-4816, 2018

      36 Lü JM, "Ginseng compounds : an update on their molecular mechanisms and medical applications" 7 : 293-302, 2009

      37 Yan HZ, "GHR is involved in gastric cell growth and apoptosis via PI3K/AKT signalling" 25 : 2450-2458, 2021

      38 Zhang G, "Function of Axl receptor tyrosine kinase in non-small cell lung cancer" 15 : 2726-2734, 2018

      39 Song RX, "Estrogen rapid action via protein complex formation involving ERalpha and Src" 16 : 347-353, 2005

      40 Yeung KT, "Epithelial-mesenchymal transition in tumor metastasis" 11 : 28-39, 2017

      41 Koopman LA, "Enapotamab vedotin, an AXL-specific antibody-drug conjugate, shows preclinical antitumor activity in non-small cell lung cancer" 4 : e128199-, 2019

      42 Hong P, "Echinatin suppresses esophageal cancer tumor growth and invasion through inducing AKT/mTOR-dependent autophagy and apoptosis" 11 : 524-, 2020

      43 Siegel RL, "Colorectal cancer statistics, 2020" 70 : 145-164, 2020

      44 Li Y, "Axl mediates tumor invasion and chemosensitivity through PI3K/Akt signaling pathway and is transcriptionally regulated by slug in breast carcinoma" 66 : 507-518, 2014

      45 Tian Y, "Anexelekto(AXL)increases resistance to EGFR-TKI and activation of AKT and ERK1/2 in non-small cell lung cancer cells" 24 : 295-303, 2016

      46 Moghimi-Dehkordi B, "An overview of colorectal cancer survival rates and prognosis in Asia" 4 : 71-75, 2012

      47 Zhao R, "Acetylshikonin suppressed growth of colorectal tumour tissue and cells by inhibiting the intracellular kinase, T-lymphokine-activated killer cell-originated protein kinase" 177 : 2303-2319, 2020

      48 Terry S, "AXL targeting overcomes human lung cancer cell resistance to NK-and CTL-mediated cytotoxicity" 7 : 1789-1802, 2019

      49 Lotsberg ML, "AXL targeting abrogates autophagic flux and induces immunogenic cell death in drug-resistant cancer cells" 15 : 973-999, 2020

      50 Zhu C, "AXL receptor tyrosine kinase as a promising anti-cancer approach : functions, molecular mechanisms and clinical applications" 18 : 153-, 2019

      51 Divine LM, "AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer" 7 : 77291-77305, 2016

      52 Axelrod HD, "AXL is a putative tumor suppressor and dormancy regulator in prostate cancer" 17 : 356-369, 2019

      53 Cardone C, "AXL is a predictor of poor survival and of resistance to anti-EGFR therapy in RAS wild-type metastatic colorectal cancer" 138 : 1-10, 2020

      54 Collina F, "AXL is a novel predictive factor and therapeutic target for radioactive iodine refractory thyroid cancer" 11 : 785-, 2019

      55 Dunne PD, "AXL is a key regulator of inherent and chemotherapy-induced invasion and predicts a poor clinical outcome in early-stage colon cancer" 20 : 164-175, 2014

      56 Kim D, "AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells" 10 : 361-, 2019

      57 Zajac O, "AXL controls directed migration of mesenchymal triple-negative breast cancer cells" 9 : 247-, 2020

      58 Abu-Thuraia A, "AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network" 11 : 3586-, 2020

      59 Zhou B, "A dynamic study on reversal of multidrug resistance by ginsenoside Rh(2)in adriamycinresistant human breast cancer MCF-7 cells" 88 : 345-351, 2012

      60 Ting Xia ; Jin Zhang ; Chuanxin Zhou ; Yu Li ; Wenhui Duan ; Bo Zhang ; Min Wang ; Jianpei Fang, "20(S)-Ginsenoside Rh2 displays effi cacy against T-cell acute lymphoblastic leukemia through the PI3K/Akt/mTOR signal pathway" 고려인삼학회 44 (44): 725-737, 2020

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-04-07 학술지명변경 한글명 : 고려인삼학회지 -> Journal of Ginseng Research KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재 1차 FAIL (등재유지) KCI등재
      2004-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2003-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2001-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 3.97 1.04 2.93
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      2.49 2.07 1.604 0.15
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