Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model
Aim. To study antitumor and anti - metastatic action of AKh-554, 2-Aminium-7-(Diethylamino)-4-(4-Metoxibenzo[d][1,3]dioxol-5-yl)-4H-chromene-3-carbonytril N-Acetylamino - ethanoate, on in vivo model of lung adenocarcinoma patient - derived xenograft model. Materials and methods. In 40 immunodeficient...
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| Format: | Article |
| Language: | Russian |
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Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
2019-06-01
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| Series: | Сеченовский вестник |
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| Online Access: | https://www.sechenovmedj.com/jour/article/view/99 |
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| author | E. A. Samishina M. O. Dudina E. V. Blinova I. R. Suslova O. N. Deryabina D. S. Blinov P. N. Zhdanov |
| author_facet | E. A. Samishina M. O. Dudina E. V. Blinova I. R. Suslova O. N. Deryabina D. S. Blinov P. N. Zhdanov |
| author_sort | E. A. Samishina |
| collection | DOAJ |
| description | Aim. To study antitumor and anti - metastatic action of AKh-554, 2-Aminium-7-(Diethylamino)-4-(4-Metoxibenzo[d][1,3]dioxol-5-yl)-4H-chromene-3-carbonytril N-Acetylamino - ethanoate, on in vivo model of lung adenocarcinoma patient - derived xenograft model. Materials and methods. In 40 immunodeficient nu/nu BALB/c female mice with heterotopic patient - derived lung adenocarcinoma xenograft model antitumor and anti - metastatic effects of 2-aminochromene derivative, AKh-554 at dose 50 mg/kg intragastrically during 7 days, were explored. Laboratory animals were randomly designated into four groups - intact mice, control, referent drug and main group. We used Cyclophosphamide as referent drug. In the tumor tissue of the animals treated with the derivative through intragastric rout we quantitively detected TUBB3, ALK and c-MET/HFG levels.Results. AKh-554 more than 7.5 times decreases both the growth rate and size of xenograft tumor when compared with control group ( p =0.001), and possesses an anti - metastatic effect. Experimental treatment up to 103±2 days increases the lifespan of tumor carriers ( p =0.001 when compared with the control; p =0.03 when compared with cyclophosphamide), and induces remission in 60% of all cases. The established effect is due to activation of tumor cells apoptosis associated with decrease in tumor tissue ALK concentration (2.77±0.54 ng/ml; p =0.001 when compared with the control and cyclophosphamide). Experimental models demonstrate no signs of pharmacological resistance to AX-554, which is confirmed by the absence of differences of c-MET/HFG tissue level in all the studied groups (0.16±0.07 ng/ml - control; 0.09±0.03 ng/ml - Cyclophosphamide; 0.10±0.04 ng/ml - AKh-554).Conclusions. AKh-554 more effectively than Cyclophosphamide inhibits xenograft tumor growth and its metastatic activity. The compound increases more than 3.3 times when compared with the control the lifespan of experimental animals and induces remission of the malignant process in 60% of tumor carriers. The compound anticancer property is due to anti-ALK-mediated activation of tumor cells’ apoptosis and suppression of cell proliferation processes. |
| first_indexed | 2024-04-10T01:20:09Z |
| format | Article |
| id | doaj.art-edaf6e87edfe47cca5191c5e7b7f6c4c |
| institution | Directory Open Access Journal |
| issn | 2218-7332 2658-3348 |
| language | Russian |
| last_indexed | 2025-03-14T12:25:38Z |
| publishDate | 2019-06-01 |
| publisher | Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University) |
| record_format | Article |
| series | Сеченовский вестник |
| spelling | doaj.art-edaf6e87edfe47cca5191c5e7b7f6c4c2025-03-02T09:29:55ZrusFederal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)Сеченовский вестник2218-73322658-33482019-06-01102142010.47093/22187332.2019.2.14-2098Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft modelE. A. Samishina0M. O. Dudina1E. V. Blinova2I. R. Suslova3O. N. Deryabina4D. S. Blinov5P. N. Zhdanov6All-Union Research Center for Biological Active Compounds SafetySechenov First Moscow State Medical University (Sechenov University)Sechenov First Moscow State Medical University (Sechenov University)All-Union Research Center for Biological Active Compounds SafetyOgarev National Research Mordovia State UniversityAll-Union Research Center for Biological Active Compounds SafetyAll-Union Research Center for Biological Active Compounds SafetyAim. To study antitumor and anti - metastatic action of AKh-554, 2-Aminium-7-(Diethylamino)-4-(4-Metoxibenzo[d][1,3]dioxol-5-yl)-4H-chromene-3-carbonytril N-Acetylamino - ethanoate, on in vivo model of lung adenocarcinoma patient - derived xenograft model. Materials and methods. In 40 immunodeficient nu/nu BALB/c female mice with heterotopic patient - derived lung adenocarcinoma xenograft model antitumor and anti - metastatic effects of 2-aminochromene derivative, AKh-554 at dose 50 mg/kg intragastrically during 7 days, were explored. Laboratory animals were randomly designated into four groups - intact mice, control, referent drug and main group. We used Cyclophosphamide as referent drug. In the tumor tissue of the animals treated with the derivative through intragastric rout we quantitively detected TUBB3, ALK and c-MET/HFG levels.Results. AKh-554 more than 7.5 times decreases both the growth rate and size of xenograft tumor when compared with control group ( p =0.001), and possesses an anti - metastatic effect. Experimental treatment up to 103±2 days increases the lifespan of tumor carriers ( p =0.001 when compared with the control; p =0.03 when compared with cyclophosphamide), and induces remission in 60% of all cases. The established effect is due to activation of tumor cells apoptosis associated with decrease in tumor tissue ALK concentration (2.77±0.54 ng/ml; p =0.001 when compared with the control and cyclophosphamide). Experimental models demonstrate no signs of pharmacological resistance to AX-554, which is confirmed by the absence of differences of c-MET/HFG tissue level in all the studied groups (0.16±0.07 ng/ml - control; 0.09±0.03 ng/ml - Cyclophosphamide; 0.10±0.04 ng/ml - AKh-554).Conclusions. AKh-554 more effectively than Cyclophosphamide inhibits xenograft tumor growth and its metastatic activity. The compound increases more than 3.3 times when compared with the control the lifespan of experimental animals and induces remission of the malignant process in 60% of tumor carriers. The compound anticancer property is due to anti-ALK-mediated activation of tumor cells’ apoptosis and suppression of cell proliferation processes.https://www.sechenovmedj.com/jour/article/view/99akh-554xenograftlung adenocarcinomaantitumor effectmechanism of actionapoptosismarkers of tumor progression |
| spellingShingle | E. A. Samishina M. O. Dudina E. V. Blinova I. R. Suslova O. N. Deryabina D. S. Blinov P. N. Zhdanov Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model Сеченовский вестник akh-554 xenograft lung adenocarcinoma antitumor effect mechanism of action apoptosis markers of tumor progression |
| title | Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model |
| title_full | Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model |
| title_fullStr | Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model |
| title_full_unstemmed | Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model |
| title_short | Antitumor action of an aminochromene derivative on human - derived lung adenocarcinoma xenograft model |
| title_sort | antitumor action of an aminochromene derivative on human derived lung adenocarcinoma xenograft model |
| topic | akh-554 xenograft lung adenocarcinoma antitumor effect mechanism of action apoptosis markers of tumor progression |
| url | https://www.sechenovmedj.com/jour/article/view/99 |
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