Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition
Ovarian cancer is the most fatal tumor characterized by an abundance of tumor-associated macrophage (TAM) infiltrations in women. Functional TAMs, which mainly present M2-like phenotypes and perform key functions on tumor progress, have been considered an attractive target for ovarian cancer therapy...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770522000894 |
| _version_ | 1818110322977800192 |
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| author | Huajiao Chen Sheng Huang Peiguang Niu Yanting Zhu Jintuo Zhou Li Jiang Danyun Li Daohua Shi |
| author_facet | Huajiao Chen Sheng Huang Peiguang Niu Yanting Zhu Jintuo Zhou Li Jiang Danyun Li Daohua Shi |
| author_sort | Huajiao Chen |
| collection | DOAJ |
| description | Ovarian cancer is the most fatal tumor characterized by an abundance of tumor-associated macrophage (TAM) infiltrations in women. Functional TAMs, which mainly present M2-like phenotypes and perform key functions on tumor progress, have been considered an attractive target for ovarian cancer therapy. Cardamonin showed an excellent antitumor activity in multiple tumor cells. This study aimed to investigate the role of cardamonin on TAMs. With the conditioned medium of ovarian cancer cells, macrophages were induced to TAMs and, accordingly, promoted the proliferation, migration, and invasion of ovarian cancer cells. Cardamonin suppressed alternatively activated (M2) polarization of TAMs and downregulated TAM-secreted tumorigenic factors, thereby hindering the pro-tumor function of TAMs on ovarian cancer cells. Moreover, cardamonin inhibited tumor growth in xenograft nude mice and lowered the expression of CD163 and CD206. Mechanistically, cardamonin inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), resulting in the suppression of M2 polarization. Furthermore, STAT3 is tightly related with mTOR activity. Altogether, these findings implied that cardamonin suppresses the pro-tumor function of TAMs by decreasing M2 polarization via mTOR inhibition, and cardamonin may be a potential therapeutic agent for ovarian cancer. |
| first_indexed | 2024-12-11T02:45:19Z |
| format | Article |
| id | doaj.art-ad55b8a5977846e2889a763a76f9d65c |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-11T02:45:19Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-ad55b8a5977846e2889a763a76f9d65c2022-12-22T01:23:27ZengElsevierMolecular Therapy: Oncolytics2372-77052022-09-0126175188Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibitionHuajiao Chen0Sheng Huang1Peiguang Niu2Yanting Zhu3Jintuo Zhou4Li Jiang5Danyun Li6Daohua Shi7Department of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR ChinaSchool of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350122, PR ChinaDepartment of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR ChinaDepartment of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR ChinaDepartment of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR ChinaDepartment of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR ChinaDepartment of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR ChinaDepartment of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR China; Corresponding author Daohua Shi, Prof., PhD, MD, Department of Pharmacy, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian 350001, PR China.Ovarian cancer is the most fatal tumor characterized by an abundance of tumor-associated macrophage (TAM) infiltrations in women. Functional TAMs, which mainly present M2-like phenotypes and perform key functions on tumor progress, have been considered an attractive target for ovarian cancer therapy. Cardamonin showed an excellent antitumor activity in multiple tumor cells. This study aimed to investigate the role of cardamonin on TAMs. With the conditioned medium of ovarian cancer cells, macrophages were induced to TAMs and, accordingly, promoted the proliferation, migration, and invasion of ovarian cancer cells. Cardamonin suppressed alternatively activated (M2) polarization of TAMs and downregulated TAM-secreted tumorigenic factors, thereby hindering the pro-tumor function of TAMs on ovarian cancer cells. Moreover, cardamonin inhibited tumor growth in xenograft nude mice and lowered the expression of CD163 and CD206. Mechanistically, cardamonin inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), resulting in the suppression of M2 polarization. Furthermore, STAT3 is tightly related with mTOR activity. Altogether, these findings implied that cardamonin suppresses the pro-tumor function of TAMs by decreasing M2 polarization via mTOR inhibition, and cardamonin may be a potential therapeutic agent for ovarian cancer.http://www.sciencedirect.com/science/article/pii/S2372770522000894cardamoninTAMsmTORSTAT3ovarian cancer |
| spellingShingle | Huajiao Chen Sheng Huang Peiguang Niu Yanting Zhu Jintuo Zhou Li Jiang Danyun Li Daohua Shi Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition Molecular Therapy: Oncolytics cardamonin TAMs mTOR STAT3 ovarian cancer |
| title | Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition |
| title_full | Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition |
| title_fullStr | Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition |
| title_full_unstemmed | Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition |
| title_short | Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition |
| title_sort | cardamonin suppresses pro tumor function of macrophages by decreasing m2 polarization on ovarian cancer cells via mtor inhibition |
| topic | cardamonin TAMs mTOR STAT3 ovarian cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2372770522000894 |
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