Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma
High-risk neuroblastoma (NB) is sensitive to chemotherapy but susceptible to chemoresistance. In this study, we aimed to analyze the incidence of chemoresistance in high-risk NB patients and to explore the role of autophagy in NB chemoresistance. We retrospectively analyzed the incidence of changing...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1019106/full |
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| author | Tingting Chen Tingting Chen Tingting Chen Chenggong Zeng Chenggong Zeng Chenggong Zeng Zhuoran Li Zhuoran Li Zhuoran Li Juan Wang Juan Wang Juan Wang Feifei Sun Feifei Sun Feifei Sun Junting Huang Junting Huang Junting Huang Suying Lu Suying Lu Suying Lu Jia Zhu Jia Zhu Jia Zhu Yizhuo Zhang Yizhuo Zhang Yizhuo Zhang Xiaofei Sun Xiaofei Sun Xiaofei Sun Zijun Zhen Zijun Zhen Zijun Zhen |
| author_facet | Tingting Chen Tingting Chen Tingting Chen Chenggong Zeng Chenggong Zeng Chenggong Zeng Zhuoran Li Zhuoran Li Zhuoran Li Juan Wang Juan Wang Juan Wang Feifei Sun Feifei Sun Feifei Sun Junting Huang Junting Huang Junting Huang Suying Lu Suying Lu Suying Lu Jia Zhu Jia Zhu Jia Zhu Yizhuo Zhang Yizhuo Zhang Yizhuo Zhang Xiaofei Sun Xiaofei Sun Xiaofei Sun Zijun Zhen Zijun Zhen Zijun Zhen |
| author_sort | Tingting Chen |
| collection | DOAJ |
| description | High-risk neuroblastoma (NB) is sensitive to chemotherapy but susceptible to chemoresistance. In this study, we aimed to analyze the incidence of chemoresistance in high-risk NB patients and to explore the role of autophagy in NB chemoresistance. We retrospectively analyzed the incidence of changing the chemotherapy regimen due to disease stabilization or disease progression during induction chemotherapy in high-risk NB patients, which was expressed as the chemoresistance rate. The autophagy levels were probed in tumor cells exposed to first-line chemotherapy agents. The sensitivity of tumor cells to chemotherapy agents and apoptosis rate were observed after inhibiting autophagy by transfection of shRNA or chloroquine (CQ). This study included 247 patients with high-risk NB. The chemoresistance rates of patients treated with cyclophosphamide + adriamycin + vincristine (CAV) alternating with etoposide + cisplatin (EP) (Group 1) and CAV alternating with etoposide + ifosfamide + cisplatin (VIP) (Group 2) was 61.5% and 39.9% (P = 0.0009), respectively. Group 2 had better survival rates than group 1. After exposure to cisplatin, cyclophosphamide, and etoposide, the autophagy-related proteins LC3-I, LC3-II, and Beclin-1 were upregulated, and the incidence of autophagy vesicle formation and the expression of P62 were increased. Chemotherapeutic agents combined with CQ significantly increased the chemotherapeutic sensitivity of tumor cells and increased the cell apoptosis. The downregulated expression of Beclin-1 increased the sensitivity of tumor cells to chemotherapeutics. Our results suggest that increasing the chemotherapy intensity can overcome resistance to NB. Inhibition of autophagy is beneficial to increase the sensitivity of NB to chemotherapy agents. |
| first_indexed | 2024-04-11T07:22:51Z |
| format | Article |
| id | doaj.art-1b42750e5e9e413d8e3267249b4b4110 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T07:22:51Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-1b42750e5e9e413d8e3267249b4b41102022-12-22T04:37:08ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10191061019106Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastomaTingting Chen0Tingting Chen1Tingting Chen2Chenggong Zeng3Chenggong Zeng4Chenggong Zeng5Zhuoran Li6Zhuoran Li7Zhuoran Li8Juan Wang9Juan Wang10Juan Wang11Feifei Sun12Feifei Sun13Feifei Sun14Junting Huang15Junting Huang16Junting Huang17Suying Lu18Suying Lu19Suying Lu20Jia Zhu21Jia Zhu22Jia Zhu23Yizhuo Zhang24Yizhuo Zhang25Yizhuo Zhang26Xiaofei Sun27Xiaofei Sun28Xiaofei Sun29Zijun Zhen30Zijun Zhen31Zijun Zhen32Department of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaDepartment of Pediatric Oncology, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaState Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, ChinaHigh-risk neuroblastoma (NB) is sensitive to chemotherapy but susceptible to chemoresistance. In this study, we aimed to analyze the incidence of chemoresistance in high-risk NB patients and to explore the role of autophagy in NB chemoresistance. We retrospectively analyzed the incidence of changing the chemotherapy regimen due to disease stabilization or disease progression during induction chemotherapy in high-risk NB patients, which was expressed as the chemoresistance rate. The autophagy levels were probed in tumor cells exposed to first-line chemotherapy agents. The sensitivity of tumor cells to chemotherapy agents and apoptosis rate were observed after inhibiting autophagy by transfection of shRNA or chloroquine (CQ). This study included 247 patients with high-risk NB. The chemoresistance rates of patients treated with cyclophosphamide + adriamycin + vincristine (CAV) alternating with etoposide + cisplatin (EP) (Group 1) and CAV alternating with etoposide + ifosfamide + cisplatin (VIP) (Group 2) was 61.5% and 39.9% (P = 0.0009), respectively. Group 2 had better survival rates than group 1. After exposure to cisplatin, cyclophosphamide, and etoposide, the autophagy-related proteins LC3-I, LC3-II, and Beclin-1 were upregulated, and the incidence of autophagy vesicle formation and the expression of P62 were increased. Chemotherapeutic agents combined with CQ significantly increased the chemotherapeutic sensitivity of tumor cells and increased the cell apoptosis. The downregulated expression of Beclin-1 increased the sensitivity of tumor cells to chemotherapeutics. Our results suggest that increasing the chemotherapy intensity can overcome resistance to NB. Inhibition of autophagy is beneficial to increase the sensitivity of NB to chemotherapy agents.https://www.frontiersin.org/articles/10.3389/fonc.2022.1019106/fullAutophagychemoresistanceneuroblastomainduction chemotherapychloroquine |
| spellingShingle | Tingting Chen Tingting Chen Tingting Chen Chenggong Zeng Chenggong Zeng Chenggong Zeng Zhuoran Li Zhuoran Li Zhuoran Li Juan Wang Juan Wang Juan Wang Feifei Sun Feifei Sun Feifei Sun Junting Huang Junting Huang Junting Huang Suying Lu Suying Lu Suying Lu Jia Zhu Jia Zhu Jia Zhu Yizhuo Zhang Yizhuo Zhang Yizhuo Zhang Xiaofei Sun Xiaofei Sun Xiaofei Sun Zijun Zhen Zijun Zhen Zijun Zhen Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma Frontiers in Oncology Autophagy chemoresistance neuroblastoma induction chemotherapy chloroquine |
| title | Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma |
| title_full | Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma |
| title_fullStr | Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma |
| title_full_unstemmed | Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma |
| title_short | Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma |
| title_sort | investigation of chemoresistance to first line chemotherapy and its possible association with autophagy in high risk neuroblastoma |
| topic | Autophagy chemoresistance neuroblastoma induction chemotherapy chloroquine |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1019106/full |
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