Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin
Abstract Background Eukaryotic translation elongation factors 1 δ (EEF1D), has garnered much attention with regards to their role in the drug resistance of cancers. In this paper, we investigated the effects and mechanisms of increasing the sensitivity of ovarian cancer cells to cisplatin or cis-dic...
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BMC
2022-06-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09699-7 |
| _version_ | 1811248089138200576 |
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| author | Qia Xu Yun Liu Shenyi Wang Jing Wang Liwei Liu Yin Xu Yide Qin |
| author_facet | Qia Xu Yun Liu Shenyi Wang Jing Wang Liwei Liu Yin Xu Yide Qin |
| author_sort | Qia Xu |
| collection | DOAJ |
| description | Abstract Background Eukaryotic translation elongation factors 1 δ (EEF1D), has garnered much attention with regards to their role in the drug resistance of cancers. In this paper, we investigated the effects and mechanisms of increasing the sensitivity of ovarian cancer cells to cisplatin or cis-dichlorodiammine platinum (DDP) by knockdown and knockout of EEF1D gene in cellular and animal models. Methods The EEF1D gene was knocked-down or -out by siRNA or CRISPR/Cas9 respectively in human ovarian cancer cell SKOV3, DDP-resistant subline SKOV3/DDP, and EEF1D gene in human primary ovarian cancer cell from 5 ovarian cancer patients with progressive disease/stable disease (PD/SD) was transiently knocked down by siRNA interference. The mice model bearing xenografted tumor was established with subcutaneous inoculation of SKOV3/DDP. Results The results show that reducing or removing EEF1D gene expression significantly increased the sensitivity of human ovarian cancer cells to DDP in inhibiting viability and inducing apoptosis in vitro and in vivo, and also boosted DDP to inhibit xenografted tumor growth. Interfering with EEF1D gene expression in mice xenografted tumor significantly affected the levels of OPTN, p-Akt, Bcl-2, Bax, cleaved caspase-3 and ERCC1 compared to DDP treated mice alone, and had less effect on PI3K, Akt and caspase-3. Conclusions The knocking down or out EEF1D gene expression could enhance the sensitivity of ovarian cancer cells to DDP partially, which may be achieved via inactivating the PI3K/AKT signaling pathway, thus inducing cell apoptosis and decreasing repairment of DNA damage. Our study provides a novel therapeutic strategy for the treatment of ovarian cancer. |
| first_indexed | 2024-04-12T15:20:42Z |
| format | Article |
| id | doaj.art-97b00dff603943d58db91f041604b48f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T15:20:42Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-97b00dff603943d58db91f041604b48f2022-12-22T03:27:26ZengBMCBMC Cancer1471-24072022-06-0122111510.1186/s12885-022-09699-7Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatinQia Xu0Yun Liu1Shenyi Wang2Jing Wang3Liwei Liu4Yin Xu5Yide Qin6Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityDepartment of Neuropsychology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical UniversityAbstract Background Eukaryotic translation elongation factors 1 δ (EEF1D), has garnered much attention with regards to their role in the drug resistance of cancers. In this paper, we investigated the effects and mechanisms of increasing the sensitivity of ovarian cancer cells to cisplatin or cis-dichlorodiammine platinum (DDP) by knockdown and knockout of EEF1D gene in cellular and animal models. Methods The EEF1D gene was knocked-down or -out by siRNA or CRISPR/Cas9 respectively in human ovarian cancer cell SKOV3, DDP-resistant subline SKOV3/DDP, and EEF1D gene in human primary ovarian cancer cell from 5 ovarian cancer patients with progressive disease/stable disease (PD/SD) was transiently knocked down by siRNA interference. The mice model bearing xenografted tumor was established with subcutaneous inoculation of SKOV3/DDP. Results The results show that reducing or removing EEF1D gene expression significantly increased the sensitivity of human ovarian cancer cells to DDP in inhibiting viability and inducing apoptosis in vitro and in vivo, and also boosted DDP to inhibit xenografted tumor growth. Interfering with EEF1D gene expression in mice xenografted tumor significantly affected the levels of OPTN, p-Akt, Bcl-2, Bax, cleaved caspase-3 and ERCC1 compared to DDP treated mice alone, and had less effect on PI3K, Akt and caspase-3. Conclusions The knocking down or out EEF1D gene expression could enhance the sensitivity of ovarian cancer cells to DDP partially, which may be achieved via inactivating the PI3K/AKT signaling pathway, thus inducing cell apoptosis and decreasing repairment of DNA damage. Our study provides a novel therapeutic strategy for the treatment of ovarian cancer.https://doi.org/10.1186/s12885-022-09699-7Human ovarian cancerEukaryotic translation elongation factors 1 δKnockdownKnockoutXenografted tumorGene expression |
| spellingShingle | Qia Xu Yun Liu Shenyi Wang Jing Wang Liwei Liu Yin Xu Yide Qin Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin BMC Cancer Human ovarian cancer Eukaryotic translation elongation factors 1 δ Knockdown Knockout Xenografted tumor Gene expression |
| title | Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin |
| title_full | Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin |
| title_fullStr | Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin |
| title_full_unstemmed | Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin |
| title_short | Interfering with the expression of EEF1D gene enhances the sensitivity of ovarian cancer cells to cisplatin |
| title_sort | interfering with the expression of eef1d gene enhances the sensitivity of ovarian cancer cells to cisplatin |
| topic | Human ovarian cancer Eukaryotic translation elongation factors 1 δ Knockdown Knockout Xenografted tumor Gene expression |
| url | https://doi.org/10.1186/s12885-022-09699-7 |
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