Overexpression of PDK4 is associated with cell proliferation, drug resistance and poor prognosis in ovarian cancer
PURPOSE: Ovarian cancer is a major type of gynecological malignancy which characterized by the chemoresistance, heterogeneity and highly metastasis. However, the mechanism underlying the progression of ovarian cancer remains elusive. Pyruvate dehydrogenase kinase family plays critical roles in tumorigenesis, and PDK4 has been demonstrated to be an oncogene in many types of cancers. The aim of this study was to identify the role of PDK4 in ovarian cancer.
METHODS: We explored the PDK4 expression according to the public database containing patients with different effect of chemotherapy. Cell proliferation and invasion assays were used to determine the function of PDK4. Mice xenograft experiment was conducted to test the pro-tumorigenesis function of PDK4 in vivo. Cell apoptosis under treatment of chemo drugs was detected by flow cytometry and TUNEL analysis. Spheroid formation assay and CD133+ cell population were used to determine the PDK4-induced stem-like traits. Immunohistochemical staining was performed to test the expression of PDK4 in ovarian cancer tissues, and Kaplan- Meier curve with log-rank test was performed to determine the association between PDK4 expression and ovarian cancer patients' prognosis.
RESULTS: Overexpression of PDK4 markedly promoted cell proliferation, invasion and tumor growth in vivo. Furthermore, PDK4 confers cell resistant to chemotherapy-induced apoptosis. Mechanically, we demonstrated that PDK4 induced stem-like traits. Meanwhile, PDK4 expression was significantly evaluated in ovarian cancer tissues compared to that in adjacent non-cancer tissues, and high expression of PDK4 was associated with poor overall survival and progression-free survival of ovarian cancer patients.
CONCLUSION: These results identify a novel role of PDK4 in regulating cell stem-like trait, which directly enhances the cell proliferation, invasion and chemoresistance in ovarian cancer, and targeting PDK4 could be a potential approach for ovarian cancer treatments.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Cancer management and research - 11(2019) vom: 20., Seite 251-262 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Jinghao [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Chemoresistance |
|---|
| Anmerkungen: |
Date Revised 31.03.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.2147/CMAR.S185015 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM292650426 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM292650426 | ||
| 003 | DE-627 | ||
| 005 | 20231225073559.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2147/CMAR.S185015 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0975.xml |
| 035 | |a (DE-627)NLM292650426 | ||
| 035 | |a (NLM)30636897 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Jinghao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Overexpression of PDK4 is associated with cell proliferation, drug resistance and poor prognosis in ovarian cancer |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 31.03.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a PURPOSE: Ovarian cancer is a major type of gynecological malignancy which characterized by the chemoresistance, heterogeneity and highly metastasis. However, the mechanism underlying the progression of ovarian cancer remains elusive. Pyruvate dehydrogenase kinase family plays critical roles in tumorigenesis, and PDK4 has been demonstrated to be an oncogene in many types of cancers. The aim of this study was to identify the role of PDK4 in ovarian cancer | ||
| 520 | |a METHODS: We explored the PDK4 expression according to the public database containing patients with different effect of chemotherapy. Cell proliferation and invasion assays were used to determine the function of PDK4. Mice xenograft experiment was conducted to test the pro-tumorigenesis function of PDK4 in vivo. Cell apoptosis under treatment of chemo drugs was detected by flow cytometry and TUNEL analysis. Spheroid formation assay and CD133+ cell population were used to determine the PDK4-induced stem-like traits. Immunohistochemical staining was performed to test the expression of PDK4 in ovarian cancer tissues, and Kaplan- Meier curve with log-rank test was performed to determine the association between PDK4 expression and ovarian cancer patients' prognosis | ||
| 520 | |a RESULTS: Overexpression of PDK4 markedly promoted cell proliferation, invasion and tumor growth in vivo. Furthermore, PDK4 confers cell resistant to chemotherapy-induced apoptosis. Mechanically, we demonstrated that PDK4 induced stem-like traits. Meanwhile, PDK4 expression was significantly evaluated in ovarian cancer tissues compared to that in adjacent non-cancer tissues, and high expression of PDK4 was associated with poor overall survival and progression-free survival of ovarian cancer patients | ||
| 520 | |a CONCLUSION: These results identify a novel role of PDK4 in regulating cell stem-like trait, which directly enhances the cell proliferation, invasion and chemoresistance in ovarian cancer, and targeting PDK4 could be a potential approach for ovarian cancer treatments | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a PDK4 | |
| 650 | 4 | |a chemoresistance | |
| 650 | 4 | |a ovarian cancer | |
| 650 | 4 | |a prognosis | |
| 650 | 4 | |a stemness | |
| 700 | 1 | |a Qian, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Meiyan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer management and research |d 2009 |g 11(2019) vom: 20., Seite 251-262 |w (DE-627)NLM197692605 |x 1179-1322 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2019 |g day:20 |g pages:251-262 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2147/CMAR.S185015 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2019 |b 20 |h 251-262 | ||