Limits...
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

Chloroquine (CQ) enhances the efficacy of cisplatin (DDP) in xenograft tumors.Tumor-bearing mice (7 animals per group) were treated by intraperitoneal injection as follows: vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days) and a combination of DDP and CQ for 18 days. (A) The tumor volume and tumor weight for each group. (B) Survival analysis of the treated mice in each group (n = 7). DDP+CQ led to a 15.5-day increase in the median survival compared with the mono-DDP treatment. (C) The body weight of mice during treatment. *p<0.05, **p<0.01, ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4414471&req=5

pone.0126147.g001: Chloroquine (CQ) enhances the efficacy of cisplatin (DDP) in xenograft tumors.Tumor-bearing mice (7 animals per group) were treated by intraperitoneal injection as follows: vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days) and a combination of DDP and CQ for 18 days. (A) The tumor volume and tumor weight for each group. (B) Survival analysis of the treated mice in each group (n = 7). DDP+CQ led to a 15.5-day increase in the median survival compared with the mono-DDP treatment. (C) The body weight of mice during treatment. *p<0.05, **p<0.01, ***p<0.001.

Mentions: To investigate whether CQ could increase the efficacy of DDP in vivo, male BALB/c nude mice (5–6 weeks old) were used as an animal model. The mice were inoculated subcutaneously with 3 millions of human hypopharyngeal FaDu cells. The mice were divided into 4 groups (n = 7) 7 days after inoculation matched for tumor volume. Mice in groups were treated with vehicle control, CQ (60mg/kg/day), DDP (5mg/kg/6days), or a combination of DDP and CQ. Mice were sacrificed after treatment for 18 days and tumor tissues were collected. We monitored the tumor volume and final tumor weight for each group (Fig 1A). The mono-CQ therapy had no impact on the tumor volume or tumor weight compared with the control group. The mono-DDP group had a decreased tumor volume (657.0±66.2 mm3) and tumor weight (0.493±0.0496 g) compared with the control group (1405.0±117.2 mm3, 0.981±0.0577 g, p<0.001 for both). The DDP+CQ treatment demonstrated a further decrease in the tumor volume (350.7±54.0 mm3) and tumor weight (0.263±0.0405 g) compared with the mono-DDP therapy (p<0.01 for both).


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)

Chloroquine (CQ) enhances the efficacy of cisplatin (DDP) in xenograft tumors.Tumor-bearing mice (7 animals per group) were treated by intraperitoneal injection as follows: vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days) and a combination of DDP and CQ for 18 days. (A) The tumor volume and tumor weight for each group. (B) Survival analysis of the treated mice in each group (n = 7). DDP+CQ led to a 15.5-day increase in the median survival compared with the mono-DDP treatment. (C) The body weight of mice during treatment. *p<0.05, **p<0.01, ***p<0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0126147.g001: Chloroquine (CQ) enhances the efficacy of cisplatin (DDP) in xenograft tumors.Tumor-bearing mice (7 animals per group) were treated by intraperitoneal injection as follows: vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days) and a combination of DDP and CQ for 18 days. (A) The tumor volume and tumor weight for each group. (B) Survival analysis of the treated mice in each group (n = 7). DDP+CQ led to a 15.5-day increase in the median survival compared with the mono-DDP treatment. (C) The body weight of mice during treatment. *p<0.05, **p<0.01, ***p<0.001.
Mentions: To investigate whether CQ could increase the efficacy of DDP in vivo, male BALB/c nude mice (5–6 weeks old) were used as an animal model. The mice were inoculated subcutaneously with 3 millions of human hypopharyngeal FaDu cells. The mice were divided into 4 groups (n = 7) 7 days after inoculation matched for tumor volume. Mice in groups were treated with vehicle control, CQ (60mg/kg/day), DDP (5mg/kg/6days), or a combination of DDP and CQ. Mice were sacrificed after treatment for 18 days and tumor tissues were collected. We monitored the tumor volume and final tumor weight for each group (Fig 1A). The mono-CQ therapy had no impact on the tumor volume or tumor weight compared with the control group. The mono-DDP group had a decreased tumor volume (657.0±66.2 mm3) and tumor weight (0.493±0.0496 g) compared with the control group (1405.0±117.2 mm3, 0.981±0.0577 g, p<0.001 for both). The DDP+CQ treatment demonstrated a further decrease in the tumor volume (350.7±54.0 mm3) and tumor weight (0.263±0.0405 g) compared with the mono-DDP therapy (p<0.01 for both).

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