ANXA2 and Rac1 negatively regulates autophagy and osteogenic differentiation in osteosarcoma cells to confer CDDP resistance
Copyright © 2023. Published by Elsevier Inc..
BACKGROUND: Cisplatin (CDDP) is a mainstay chemotherapeutic agent for OS treatment, but drug resistance has become a hurdle to limit its clinical effect. Autophagy plays an important role in CDDP resistance in OS, and in the present study we explored the role of ANXA2 and Rac1 in dictating CDDP sensitivity in OS cells.
METHODS: ANXA2 and Rac1 expression levels were examined by Western blot and autophagy induction was detected by transmission electron miscroscope (TEM) in the clinical samples and OS cell lines. CDDP resistant cells were established by exposing OS cells to increasing doses of CDDP. The effects of ANXA2 and Rac1 knockdown on CDDP sensitivity were evaluated in the cell and animal models.
RESULTS: Reduced autophagy was associated with the increased expression of ANXA2 and Rac1 in CDDP resistant OS tumor samples and cells. Autophagy suppression promoted CDDP resistance and inducing autophagy re-sensitized the resistant cells to CDDP treatment in vitro and in vivo. Further, knocking down ANXA2 or Rac1 re-activated autophagy and attenuated CDDP resistance in OS cells. We further demonstrated that CDDP resistant OS cells displayed a poorer osteogenic differentiation state when compared to the parental cell lines, which was significantly reversed by autophagy re-activation and ANXA2 or Rac1 silencing.
CONCLUSION: Our findings revealed a complicated interplay of ANXA2/Rac1, autophagy induction, and osteogenic differentiation in dictating CDDP resistance in OS cells, suggesting ANXA2 and Rac1 as promising targets to modulate autophagy and overcome CDDP resistance in OS cells.
| Errataetall: |
ErratumIn: Biochem Biophys Res Commun. 2024 Feb 23;704:149487. - PMID 38401302 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:676 |
|---|---|
| Enthalten in: |
Biochemical and biophysical research communications - 676(2023) vom: 08. Okt., Seite 198-206 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pan, Baolong [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ANXA2 and Rac1 |
|---|
| Anmerkungen: |
Date Completed 04.09.2023 Date Revised 24.02.2024 published: Print-Electronic ErratumIn: Biochem Biophys Res Commun. 2024 Feb 23;704:149487. - PMID 38401302 Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bbrc.2023.07.006 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36035923X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36035923X | ||
| 003 | DE-627 | ||
| 005 | 20240229151443.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bbrc.2023.07.006 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1305.xml |
| 035 | |a (DE-627)NLM36035923X | ||
| 035 | |a (NLM)37536195 | ||
| 035 | |a (PII)S0006-291X(23)00854-9 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pan, Baolong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ANXA2 and Rac1 negatively regulates autophagy and osteogenic differentiation in osteosarcoma cells to confer CDDP resistance |
| 264 | 1 | |c 2023 | |
| 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 Completed 04.09.2023 | ||
| 500 | |a Date Revised 24.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ErratumIn: Biochem Biophys Res Commun. 2024 Feb 23;704:149487. - PMID 38401302 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Inc. | ||
| 520 | |a BACKGROUND: Cisplatin (CDDP) is a mainstay chemotherapeutic agent for OS treatment, but drug resistance has become a hurdle to limit its clinical effect. Autophagy plays an important role in CDDP resistance in OS, and in the present study we explored the role of ANXA2 and Rac1 in dictating CDDP sensitivity in OS cells | ||
| 520 | |a METHODS: ANXA2 and Rac1 expression levels were examined by Western blot and autophagy induction was detected by transmission electron miscroscope (TEM) in the clinical samples and OS cell lines. CDDP resistant cells were established by exposing OS cells to increasing doses of CDDP. The effects of ANXA2 and Rac1 knockdown on CDDP sensitivity were evaluated in the cell and animal models | ||
| 520 | |a RESULTS: Reduced autophagy was associated with the increased expression of ANXA2 and Rac1 in CDDP resistant OS tumor samples and cells. Autophagy suppression promoted CDDP resistance and inducing autophagy re-sensitized the resistant cells to CDDP treatment in vitro and in vivo. Further, knocking down ANXA2 or Rac1 re-activated autophagy and attenuated CDDP resistance in OS cells. We further demonstrated that CDDP resistant OS cells displayed a poorer osteogenic differentiation state when compared to the parental cell lines, which was significantly reversed by autophagy re-activation and ANXA2 or Rac1 silencing | ||
| 520 | |a CONCLUSION: Our findings revealed a complicated interplay of ANXA2/Rac1, autophagy induction, and osteogenic differentiation in dictating CDDP resistance in OS cells, suggesting ANXA2 and Rac1 as promising targets to modulate autophagy and overcome CDDP resistance in OS cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ANXA2 and Rac1 | |
| 650 | 4 | |a Autophgy | |
| 650 | 4 | |a Cisplatin (CDDP) | |
| 650 | 4 | |a Drug resistance | |
| 650 | 4 | |a Osteogenic differentiation | |
| 650 | 4 | |a Osteosarcoma (OS) | |
| 650 | 7 | |a Cisplatin |2 NLM | |
| 650 | 7 | |a Q20Q21Q62J |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 700 | 1 | |a Pan, Yanyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shuangneng |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Yingying |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xuemei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jianping |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biochemical and biophysical research communications |d 1960 |g 676(2023) vom: 08. Okt., Seite 198-206 |w (DE-627)NLM000000035 |x 1090-2104 |7 nnns |
| 773 | 1 | 8 | |g volume:676 |g year:2023 |g day:08 |g month:10 |g pages:198-206 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbrc.2023.07.006 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 676 |j 2023 |b 08 |c 10 |h 198-206 | ||