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Chloroquine-enhanced efficacy of cisplatin in the treatment of hypopharyngeal carcinoma in xenograft mice.

Zhao XG, Sun RJ, Yang XY, Liu DY, Lei DP, Jin T, Pan XL - PLoS ONE (2015)

Bottom Line: However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC.Chloroquine (CQ) has been reported to enhance the effectiveness of chemotherapy and radiotherapy in liver, pancreas, breast, prostate and colon tumors, but it is unclear whether CQ could increase the efficacy of DDP for treating HSCC.Inhibition of autophagy markedly enhanced the DDP-induced antitumor effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.

ABSTRACT
Hypopharyngeal squamous cell carcinoma (HSCC) has the worst prognosis among head and neck cancers. Cisplatin (DDP)-based chemotherapy is an important part of multimodal treatments. However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC. Chloroquine (CQ) has been reported to enhance the effectiveness of chemotherapy and radiotherapy in liver, pancreas, breast, prostate and colon tumors, but it is unclear whether CQ could increase the efficacy of DDP for treating HSCC. We inoculated BALB/c nude mice with a subcutaneous injection of human hypopharyngeal FaDu cells to generate our animal model. Mice were randomly divided into 4 groups and treated with vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days), or a combination of DDP and CQ. Tumor growth and survival of the mice were monitored. We found that CQ inhibited autophagy and increased DDP-induced apoptosis in the xenograft mouse model. CQ enhanced the efficacy of DDP, resulting in decreased tumor growth and prolonged survival of the mice. To test whether blocking autophagy enhanced the efficacy of DDP, FaDu cells were infected with lentiviral shRNA to Beclin-1 and inoculated into the flanks of nude mice. Inhibition of autophagy markedly enhanced the DDP-induced antitumor effect. Our study suggests that the addition of CQ to DDP-based chemotherapy could be a potential therapeutic strategy for treating HSCC, and the inhibition of autophagy may contribute to chemotherapy sensitization in HSCC.

No MeSH data available.


Related in: MedlinePlus

Delayed effects of autophagy inhibition by CQ in xenograft tumors.Tumors treated with CQ (60 mg/kg/day) were collected after treatment for 1, 3 and 7 days and sectioned for LC3 immunohistochemistry. Scale bar = 20 μm.
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pone.0126147.g005: Delayed effects of autophagy inhibition by CQ in xenograft tumors.Tumors treated with CQ (60 mg/kg/day) were collected after treatment for 1, 3 and 7 days and sectioned for LC3 immunohistochemistry. Scale bar = 20 μm.

Mentions: To confirm the time needed for inhibition of autophagy, tumor bearing mice treated with CQ (60 mg/kg/day) were sacrificed after consecutive administrations for 1, 3 and 7 days separately. Tumor tissues were sectioned for LC3 Immunohistochemistry (Fig 5). LC3 accumulation on day 1 and 3 was rare. A marked accumulation of LC3 was observed after CQ administration for 7 consecutive days, suggesting an autophagy inhibition effect by CQ till day 7.


Chloroquine-enhanced efficacy of cisplatin in the treatment of hypopharyngeal carcinoma in xenograft mice.

Zhao XG, Sun RJ, Yang XY, Liu DY, Lei DP, Jin T, Pan XL - PLoS ONE (2015)

Delayed effects of autophagy inhibition by CQ in xenograft tumors.Tumors treated with CQ (60 mg/kg/day) were collected after treatment for 1, 3 and 7 days and sectioned for LC3 immunohistochemistry. Scale bar = 20 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414471&req=5

pone.0126147.g005: Delayed effects of autophagy inhibition by CQ in xenograft tumors.Tumors treated with CQ (60 mg/kg/day) were collected after treatment for 1, 3 and 7 days and sectioned for LC3 immunohistochemistry. Scale bar = 20 μm.
Mentions: To confirm the time needed for inhibition of autophagy, tumor bearing mice treated with CQ (60 mg/kg/day) were sacrificed after consecutive administrations for 1, 3 and 7 days separately. Tumor tissues were sectioned for LC3 Immunohistochemistry (Fig 5). LC3 accumulation on day 1 and 3 was rare. A marked accumulation of LC3 was observed after CQ administration for 7 consecutive days, suggesting an autophagy inhibition effect by CQ till day 7.

Bottom Line: However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC.Chloroquine (CQ) has been reported to enhance the effectiveness of chemotherapy and radiotherapy in liver, pancreas, breast, prostate and colon tumors, but it is unclear whether CQ could increase the efficacy of DDP for treating HSCC.Inhibition of autophagy markedly enhanced the DDP-induced antitumor effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.

ABSTRACT
Hypopharyngeal squamous cell carcinoma (HSCC) has the worst prognosis among head and neck cancers. Cisplatin (DDP)-based chemotherapy is an important part of multimodal treatments. However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC. Chloroquine (CQ) has been reported to enhance the effectiveness of chemotherapy and radiotherapy in liver, pancreas, breast, prostate and colon tumors, but it is unclear whether CQ could increase the efficacy of DDP for treating HSCC. We inoculated BALB/c nude mice with a subcutaneous injection of human hypopharyngeal FaDu cells to generate our animal model. Mice were randomly divided into 4 groups and treated with vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days), or a combination of DDP and CQ. Tumor growth and survival of the mice were monitored. We found that CQ inhibited autophagy and increased DDP-induced apoptosis in the xenograft mouse model. CQ enhanced the efficacy of DDP, resulting in decreased tumor growth and prolonged survival of the mice. To test whether blocking autophagy enhanced the efficacy of DDP, FaDu cells were infected with lentiviral shRNA to Beclin-1 and inoculated into the flanks of nude mice. Inhibition of autophagy markedly enhanced the DDP-induced antitumor effect. Our study suggests that the addition of CQ to DDP-based chemotherapy could be a potential therapeutic strategy for treating HSCC, and the inhibition of autophagy may contribute to chemotherapy sensitization in HSCC.

No MeSH data available.


Related in: MedlinePlus