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Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways.

Wang YC, Wu YN, Wang SL, Lin QH, He MF, Liu QL, Wang JH - Int. J. Gynecol. Cancer (2016)

Bottom Line: The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish.Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner.Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01).

View Article: PubMed Central - PubMed

Affiliation: *Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, Nanjing Medical University; †China Pharmaceutical University; ‡Nanjing University of Technology School of Pharmaceutical Science; §Department of Obstetrics and Gynecology, Jiangning Hospital, Nanjing Medical University; and ∥Jinling Hospital, Nanjing University, Nanjing, China.

ABSTRACT

Objective: We investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3).

Methods: Cytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish.

Results: Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01).

Conclusions: Docosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy.

No MeSH data available.


Related in: MedlinePlus

The effects of ALA and DHA on metastasis of HO8910 cells in model of transgenic zebrafishes. A, 200 cells were injected into the yolk sac of transgenic zebrafishes at 48 hpf per fish, which were pretreated with 120 μM ALA and DHA for 72 hours. A fluorescence microscopy was used to observe dissemination of HO8910 cells in zebrafishes 5 dpi. Green fluorescence shows vasculature of transgenic zebrafish, red fluorescence representing HO8910 cells. B, The metastasis rate and survival rate of zebrafishes was shown by histogram. These experiments were performed in triplicate, and the results showed 1 of 3 independent experiments (***P < 0.005 compared with the control). ALA was used as isotype control. Two percent PVP was used as pharmaceutic adjuvant to prevent cell clumping and needle clogging, and also as a control.
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Figure 5: The effects of ALA and DHA on metastasis of HO8910 cells in model of transgenic zebrafishes. A, 200 cells were injected into the yolk sac of transgenic zebrafishes at 48 hpf per fish, which were pretreated with 120 μM ALA and DHA for 72 hours. A fluorescence microscopy was used to observe dissemination of HO8910 cells in zebrafishes 5 dpi. Green fluorescence shows vasculature of transgenic zebrafish, red fluorescence representing HO8910 cells. B, The metastasis rate and survival rate of zebrafishes was shown by histogram. These experiments were performed in triplicate, and the results showed 1 of 3 independent experiments (***P < 0.005 compared with the control). ALA was used as isotype control. Two percent PVP was used as pharmaceutic adjuvant to prevent cell clumping and needle clogging, and also as a control.

Mentions: To further elucidate the effect of ALA and DHA on metastasis of human ovarian cancer cells, the aggressive ability of HO8910 cells was assayed. We evaluated the optimal number (200 cells injected per fish). The cancer cell dissemination was considered as migration if the cells were beyond the boundaries with the heart cavity frontally, on top of the swim bladder dorsally and beyond the urogenital opening caudally. After 5 days, approximately 40% of the zebrafishes injected by HO8910 cells displayed metastasis phenotype, and approximately 35% of the zebrafishes injected by HO8910 cells pretreated with 120 μM ALA displayed metastasis phenotype (Fig. 5B). As shown in Figure 5A, HO8910 cells untreated with DHA migrated to the head, blood vessels, and the tail part; while pretreated with 120 μM DHA for 72 hours, cells were jailed in the injection site or within the boundaries without migration phenotype. The 5 days survival rate of zebrafishes injected cells were both approximately 85% in groups treated with or without ALA or DHA, however, 90% in 2% PVP group. There was no statistically significant difference in survival rate among groups; however, there was statistically significant difference in the metastasis rate between the groups treated with or without DHA (P < 0.005) (Fig. 5B).


Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways.

Wang YC, Wu YN, Wang SL, Lin QH, He MF, Liu QL, Wang JH - Int. J. Gynecol. Cancer (2016)

The effects of ALA and DHA on metastasis of HO8910 cells in model of transgenic zebrafishes. A, 200 cells were injected into the yolk sac of transgenic zebrafishes at 48 hpf per fish, which were pretreated with 120 μM ALA and DHA for 72 hours. A fluorescence microscopy was used to observe dissemination of HO8910 cells in zebrafishes 5 dpi. Green fluorescence shows vasculature of transgenic zebrafish, red fluorescence representing HO8910 cells. B, The metastasis rate and survival rate of zebrafishes was shown by histogram. These experiments were performed in triplicate, and the results showed 1 of 3 independent experiments (***P < 0.005 compared with the control). ALA was used as isotype control. Two percent PVP was used as pharmaceutic adjuvant to prevent cell clumping and needle clogging, and also as a control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920273&req=5

Figure 5: The effects of ALA and DHA on metastasis of HO8910 cells in model of transgenic zebrafishes. A, 200 cells were injected into the yolk sac of transgenic zebrafishes at 48 hpf per fish, which were pretreated with 120 μM ALA and DHA for 72 hours. A fluorescence microscopy was used to observe dissemination of HO8910 cells in zebrafishes 5 dpi. Green fluorescence shows vasculature of transgenic zebrafish, red fluorescence representing HO8910 cells. B, The metastasis rate and survival rate of zebrafishes was shown by histogram. These experiments were performed in triplicate, and the results showed 1 of 3 independent experiments (***P < 0.005 compared with the control). ALA was used as isotype control. Two percent PVP was used as pharmaceutic adjuvant to prevent cell clumping and needle clogging, and also as a control.
Mentions: To further elucidate the effect of ALA and DHA on metastasis of human ovarian cancer cells, the aggressive ability of HO8910 cells was assayed. We evaluated the optimal number (200 cells injected per fish). The cancer cell dissemination was considered as migration if the cells were beyond the boundaries with the heart cavity frontally, on top of the swim bladder dorsally and beyond the urogenital opening caudally. After 5 days, approximately 40% of the zebrafishes injected by HO8910 cells displayed metastasis phenotype, and approximately 35% of the zebrafishes injected by HO8910 cells pretreated with 120 μM ALA displayed metastasis phenotype (Fig. 5B). As shown in Figure 5A, HO8910 cells untreated with DHA migrated to the head, blood vessels, and the tail part; while pretreated with 120 μM DHA for 72 hours, cells were jailed in the injection site or within the boundaries without migration phenotype. The 5 days survival rate of zebrafishes injected cells were both approximately 85% in groups treated with or without ALA or DHA, however, 90% in 2% PVP group. There was no statistically significant difference in survival rate among groups; however, there was statistically significant difference in the metastasis rate between the groups treated with or without DHA (P < 0.005) (Fig. 5B).

Bottom Line: The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish.Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner.Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01).

View Article: PubMed Central - PubMed

Affiliation: *Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, Nanjing Medical University; †China Pharmaceutical University; ‡Nanjing University of Technology School of Pharmaceutical Science; §Department of Obstetrics and Gynecology, Jiangning Hospital, Nanjing Medical University; and ∥Jinling Hospital, Nanjing University, Nanjing, China.

ABSTRACT

Objective: We investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3).

Methods: Cytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish.

Results: Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01).

Conclusions: Docosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy.

No MeSH data available.


Related in: MedlinePlus