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Journal of Chinese Integrative Medicine ›› 2009, Vol. 7 ›› Issue (8): 758-514.doi: 10.3736/jcim20090810

• Original Experimental Research • Previous Articles     Next Articles

Effects of Compound Zhebei Granule plus doxorubicin on mdr1 gene expression in nude mice with K562/A02 tumor xenografts

Zhi Zheng , Ju Chen, Dong-yun Li, Xin-yi Chen   

  1. Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine^ Beijing 100700, China
  • Received:2009-04-27 Accepted:2009-06-22 Online:2009-08-20 Published:2009-08-15
  • Contact: Xin-yi Chen E-mail:chenxinyi0729@sohu.com

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Objective

To investigate the effects of Compound Zhebei Granule (CZBG), a compound traditional Chinese herbal medicine, combined with adriamycin (ADM) on mdr1 gene expression in tumor xenografts in nude mice.

Methods

A tumor xenografts model was established by subcutaneously injecting multidrug resistance cell line K562/A02 into the axillary flank of BALB/c-nu mice. Sixty tumor-bearing nude mice were divided into untreated group, ADM group and high-, medium-, and low-dose CZBG plus ADM groups. The nude mice in the CZBG plus ADM groups were intragastrically administered with CZBG once per day and intraperitoneally injected with ADM once every other day. The nude mice in the untreated group and the ADM group were administered with normal saline or ADM respectively. The course of treatment was continuous for 14 days. The weight of tumor xenografts was measured after treatment and the inhibition rate of tumor xenografts was calculated. The mdr1 gene expression in tumor xenografts was tested by quantitative polymerase chain reaction method. 

Results

Compared with the untreated group, CZBG (high-, medium- and low-dose) plus ADM could significantly decrease the weight of tumor xenografts in nude mice (P<0.05). Compared with ADM, high- and medium-dose CZBG plus ADM could decrease the weight of tumor xenografts in nude mice with statistical significance (P<0.05). The high- and medium-dose CZBG plus ADM could also significantly decrease the mdr1 gene expression in tumor xenografts as compared with ADM alone (P<0.05). 

Conclusion

CZBG at high- and medium-dose plus ADM can inhibit the growth of tumor xenografts and decrease the mdr1 gene expression in tumor xenografts in nude mice.

Key words: Compound Zhebei Granule, Multidrug resistance, K562/A02 cell line, Tumor xenograft, Mdr1, Mice, Nude

Table 1

Tumor weight and inhibition rate of tumor xenografts in different groups"

Group n Tumor weight
($\bar{x}$±s, g)		 IR (%)
Untreated 9 1.413±0.676 0
ADM 9 1.000±0.589 28.66
Low-dose CZBG plus ADM 10 1.057±0.613 25.18
Medium-dose CZBG plus ADM 9 0.728±0.428△ 48.42
High-dose CZBG plus ADM 9 0.418±0.295△ 70.35

Figure 1

Fluorescent quantitation PCR kinetics curves of mdr1 gene and internal reference gene abl in tumor xenografts in different groups a: Fluorescent quantitation PCR kinetics curves of the high-, medium- and low-dose CZBG groups; b: Fluorescent quantitation PCR kinetics curves of the ADM group and untreated group."

Table 2

Ct value of mdr1 gene expression in tumor xenografts in different groups ($\bar{x}$±s)"

Group n Ct (mdr1) Ct (abl) ΔCt (Ctmdr1–Ctabl) ΔΔCt (ΔCt–ΔCtcontrol) Normalized 2–ΔΔCt
Untreated 5 20.60±1.07 27.24±1.07 –6.64±0.24 –0.03±0.23 1.03±0.17
ADM 5 21.22±1.07 28.00±0.62 –6.78±0.47 –0.17±0.47 1.17±0.36
Low-dose CZBG plus ADM 5 20.17±1.75 27.15±1.34 –6.98±0.41 –0.37±0.41 1.32±0.40
Medium-dose CZBG plus ADM 5 20.43±1.39 26.11±0.67 –5.67±1.00 0.93±0.39 0.64±0.10*△
High-dose CZBG plus ADM 5 19.78±1.82 26.46±1.85 –6.68±0.33 –0.075±0.33 1.07±0.26△
Calibrator model 5 21.77 28.38 –6.61 0 1
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