Adjuvant Therapy of Breast Cancer with Pirarubicin Versus Epirubicin in Combination with Cyclophosphamide and 5-fluorouracil

Li, Jun Jie; Di, Gen-Hong; Tang, Li; Yu, Ke; Hu, Zhen; Liu, Guang Yu; Lu, Junyan; Wu, Jiong; Han, Qi; Shen, Zhen; Shao, Zhi Ming

doi:10.1111/j.1524-4741.2011.01158.x

Cited by 5 publications

(10 citation statements)

References 9 publications

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“…24 Moreover, THP and THP-based combination therapies are effective against various tumors without severe side effects in the clinic. [25][26][27][28] However, a previous study demonstrated that most of patients with cervical cancer were not sensitive to THP treatment. 5 An optimized dose of 60 mg of THP (approximately 180 ng/ml in blood) only has a 13.3% response rate in clinic.…”

Section: Discussionmentioning

confidence: 99%

Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin

Yan

et al. 2016

Autophagy

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Pirarubicin (THP) is a newer generation anthracycline anticancer drug. In the clinic, THP and THP-based combination therapies have been demonstrated to be effective against various tumors without severe side effects. However, previous clinical studies have shown that most patients with cervical cancer are not sensitive to THP treatment, and the associated mechanisms are not clear. Consistent with the clinical study, we confirmed that cervical cancer cells were resistant to THP in vitro and in vivo. Our data demonstrated that THP induced a protective macroautophagy/autophagy response in cervical cancer cells, and suppression of this autophagy dramatically enhanced the cytotoxicity of THP. By scanning the mRNA level change of autophagy-related genes, we found that the upregulation of ATG4B (autophagyrelated 4B cysteine peptidase) plays an important role in THP-induced autophagy. Moreover, THP increased the mRNA level of ATG4B in cervical cancer cells by promoting mRNA stability without influencing its transcription. Furthermore, THP triggered a downregulation of MIR34C-5p, which was associated with the upregulation of ATG4B and autophagy induction. Overexpression of MIR34C-5p significantly decreased the level of ATG4B and attenuated autophagy, accompanied by enhanced cell death and apoptosis in THP-treated cervical cancer cells. These results for the first time reveal the presence of a MIR34C-5p-ATG4B-autophagy signaling axis in THP-treated cervical cancer cells in vitro and in vivo, and the axis, at least partially, accounts for the THP nonsensitivity in cervical cancer patients. This study may provide a new insight for improving the chemotherapeutic effect of THP, which may be beneficial to the further clinical application of THP in cervical cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin

Yan

et al. 2016

Autophagy

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“…These results suggest that THP partially overcomes the resistance caused by overexpression of P-gp and that THP may play an important role in treatment of patients with refractory or recurrent high-grade osteosarcoma. In fact, THP has also shown favorable activity in various types of cancer cells, including P-gp overexpressing breast cancer [27] , ADM-resistant lymphoblastoma [28] , MG-63 cells [29] and bladder cancers [30] in vitro, and has substantial clinical activity against various tumors without severe side effects [4][5][6][7]15,16] . Despite the ability of THP to overcome MDR in clinical studies [6,16,17] , very little is known about THP-induced cytotoxicity and the underlying mechanisms of pirarubicin on MDR osteosarcoma cells.…”

Section: Wwwnaturecom/aps Zheng Se Et Almentioning

confidence: 99%

“…Recently, pirarubicin (THP), a novel anthracycline derivative of ADM, has been used clinically to treat tumors such as osteosarcoma, breast cancer, lymphoma and acute myeloid leukemia [4][5][6][7] . Moreover, THP has shown a greater antitumor activity [8][9][10] and lower cardiotoxicity [11] than ADM.…”

Section: Introductionmentioning

confidence: 99%

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

et al. 2012

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Aim: Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP were explored. Methods: Human osteosarcoma cell line MG63 and human MDR osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was examined using a cell proliferation assay with the Cell Counting Kit-8 (CCK-8). The distribution of cells across the cell cycle was determined with flow cytometry. The expression of cell cycle-regulated genes cyclin B1 and Cdc2 (CDK1), and the phosphorylated Cdc2 and Cdc25C was examined using Western blot analyses. Results: MG63/DOX cells were highly resistant to doxorubicin (ADM) and gemcitabine (GEM), but were sensitive or lowly resistant to THP, methotrexate (MTX) and cisplatin (DDP). Treatment of MG63/DOX cells with THP (200-1000 ng/mL) inhibited the cell proliferation in time-and concentration-dependent manners. THP (50-500 ng/mL) induced MG63/DOX cell cycle arrest at the G 2 /M phase in time-and concentration-dependent manners. Furthermore, the treatment of MG63/DOX cells with THP (200-1000 ng/mL) downregulated cyclin B1 expression, and decreased the phosphorylated Cdc2 at Thr 161 . Conversely, the treatment increased the phosphorylated Cdc2 at Thr 14 /Tyr 15 and Cdc25C at Ser 216 , which led to a decrease in Cdc2-cyclin B1 activity. Conclusion: The cytotoxicity of THP to MG63/DOX cells may be in part due to its ability to arrest cell cycle progression at the G 2 /M phase, which supports the use of THP for managing patients with MDR osteosarcoma.

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“…Existing NACT protocols often include docetaxel, anthracycline, cyclophosphamide, and trastuzumab, which are effective in treatment of BC [21]. Notably, anthracyclines, such as pirarubicin (THP) and epirubicin (EPI), are standard combinations in NACT regimen in BC [22]. THP and EPI treatment correlates with significantly elevated disease-free and overall survival in BC [23].…”

Section: Introductionmentioning

confidence: 98%

“…THP has improved antitumor activity and lower acute cardiotoxicity, with a response rate of 23.2 % in advanced BC [24]. EPI is one of the most frequently used chemotherapy agents in BC treatment because of its fewer side effects, e.g., lower cardiac toxicity than doxorubicin or mitoxantrone [22]. The efficacy of combination therapy is generally better than single-agent chemotherapy in many aspects, including higher overall survival in BC patients [25].…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant chemotherapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and docetaxel

Shi

Wei

et al. 2015

Tumor Biol.

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Breast cancers (BC) are treated with surgery, radiotherapy, and chemotherapy. Neoadjuvant chemotherapy (NACT) is an emerging treatment option in many cancers and is given before primary therapy to shrink tumor size. The efficacy of NACT in varied settings of BC, such as inoperable tumors, borderline resectable tumors, and breast-conserving surgery, has been debated extensively in literature, and the results remain unclear and depended on a wide variety of factors such as cancer type, disease extent, and the specific combination of chemotherapy drugs. This study was performed to examine the efficacy, toxicity, and tolerability of pirarubicin (THP) and epirubicin (EPI) in combination with docetaxel and cyclophosphamide in a NACT setting for BC. A total of 48 patients with stage II or III breast cancers were randomly divided into two groups: THP group and EPI group. The patients in THP group received 2-4 cycles of neoadjuvant chemotherapy with DTC regimen (docetaxel, THP, cyclophosphamide), while patients in the EPI group received 2-4 cycles of DEC regimen (docetaxel, EPI, cyclophosphamide) before surgery. The incidence of adverse reactions and the efficacy of the treatment regimen were compared between the two groups. Prognostic evaluation indexes were estimated by Kaplan-Meier survival analysis, including the 5-year disease-free survival (DFS) and overall survival (OS). The overall response rate in THP group was 83.3 %, and the EPI group showed a response rate of 79.2 %, with no statistically significant difference in response rate between the two groups. The incidence of cardiac toxicity, myelosuppression, nausea, and vomiting in the THP group was significantly lower than the EPI group (all P < 0.05). The incidence of hepatic toxicity, alopecia, and diarrhea in the THP group was also lower than the EPI group, but these differences were not statistically significant. The 5-year DFS and OS in THP versus EPI groups were 80 versus 76 % (DFS) and 86 versus 81 % (OS), respectively. Our study found that NACT with DTC regimen and DEC regimen were both very effective in treatment of BC. However, THP-based combination therapy was associated with significantly lower incidence of cardiac toxicity, myelosuppression, nausea, and vomiting.

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Adjuvant Therapy of Breast Cancer with Pirarubicin Versus Epirubicin in Combination with Cyclophosphamide and 5-fluorouracil

Cited by 5 publications

References 9 publications

Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin

Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

Neoadjuvant chemotherapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and docetaxel

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