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Journal of Chinese Integrative Medicine ›› 2006, Vol. 4 ›› Issue (3): 275-280.doi: 10.3736/jcim20060311

• Original Experimental Research • Previous Articles     Next Articles

Effects of Jinlongshe Granules on apoptosis of MKN-45 human gastric cancer cells orthotopically transplanted in nude mice

Zhi-hong Yu, Pin-kang Wei, Ling Xu, Zhi-feng Qin, Jun Shi, Yan Xiao, Hui-ming Lin   

  1. Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
  • Online:2006-05-31 Published:2006-05-15

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Objective

To assess the effects of Jinlongshe Granules (JLSG) on tumor growth of gastric carcinoma.

Methods

Fifty nude mice orthotopically transplanted with MKN-45 human gastric cancer cells were divided into five groups: untreated group, 5-fluorouracil (5-FU)-treated group and high-, medium-, and low-dose JLSG-treated groups. Corresponding antitumor drugs were administered in each group except the untreated group. The antitumor effects in vivo were evaluated. Cell cycle distribution and apoptosis of MKN-45 human gastric cancer cells were determined by using flow cytometry (FCM) and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining assay. The ultrastructure of MKN-45 gastric cancer cells was observed by transmission electron microscope.

Results

In the mice treated with high-, medium-, and low-dose JLSG, the growth inhibition rates of gastric cancer were 68.13%, 55.94% and 50.31% respectively, and this antitumor effect was dose-dependent. In the mice treated with intraperitoneal injection of 5-FU, the growth inhibition rate of gastric cancer was 53.43% and not much different from those treated with JLSG. The apoptotic rates in the high-, medium-, and low-dose JLSG-treated groups were 22.81%, 28.27% and 38.54% respectively, in a dose-dependent manner, with the cell cycle arrested at G0/G1 phase. An Annexin V-FITC/PI staining assay revealed that the percentages of early apoptotic cells in the three dose JLSG-treated groups were all significantly higher than that in the 5-FU-treated group, whereas the late apoptotic and necrotic cells were much more in the 5-FU-treated group than those in the three dose JLSG-treated groups.

Conclusion

Jinlongshe Granules exert an inhibiting effect on MKN-45 human gastric cancer cells orthotopically transplanted in nude mice by promoting the cell apoptosis.

Key words: Jinlongshe Granules, Stomach neoplasms, Orthotopic transplantation, Cell cycle, Apoptosis, Traditional Chinese medicine and pharmacy, Nude mouse, Huma

CLC Number: 

  • R735.2

Table 1

Antitumor effects on orthotopically transplanted gastric cancer in nude mice in different groups（ヌ±S ）"

Group n Tumor weight (?x±s, g) Growth inhibition rate (%)
Untreated 10 3.20±0.96 –
High-dose JLSG-treated 10 1.02±0.57** 68.13
Medium-dose JLSG-treated 10 1.41±1.39** 55.94
Low-dose JLSG-treated 10 1.59±1.12** 50.31
5-FU-treated 8 1.49±1.37** 53.43

Figure 1

Ultrastructures of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groupsA: Untreated group (×4 000); B: Medium-dose JLSG-treated group (×6 000); C: 5-FU-treated group (×3 000)."

Table 2

Cell cycle distribution and apoptotic rate of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groups （ヌ±S ）"

Group n G0/G1 G2/M S Apoptotic rate
Untreated 10 42.40±11.28 21.28±11.43 36.92±12.21 19.88±14.83△
High-dose JLSG-treated 10 50.58±8.78 26.45±12.53 14.56±9.35* 38.54±12.65
Medium-dose JLSG-treated 10 47.55±7.02 26.51±15.05 19.36±12.69* 28.27±11.25
Low-dose JLSG-treated 10 46.37±12.09 25.47±14.79 24.04±13.27* 22.81±10.65△
5-FU-treated 8 41.78±4.30 23.59±11.97 19.97±13.31* 24.97±9.93△

Figure 2

Classification percentage of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groups by Annexin V-FITC/PI staining assay and flow cytometryA: High-dose JLSG-treated group; B: Medium-dose JLSG-treated group; C: Low-dose JLSG-treated group;D: Untreated group; E: 5-FU-treated group."

Table 3

Classification percentage of MKN-45 gastric cancer cells orthotopically transplanted in nude mice in different groups by Annexin V-FITC/PI staining assay and flow cytometry (ヌ±S, %)"

Group n Damaged cells Late apoptotic cells and Living cells Early apoptotic
(in LUQ) necrotic cells (in RUQ) (in LLQ) cells (in RLQ)
Untreated 10 22.19±7.73 12.58±6.94 63.99±6.36 1.56±1.37△
High-dose JLSG-treated 10 26.26±2.29 11.76±2.72 50.12±4.53* 12.21±4.45*
Medium-dose JLSG-treated 10 27.25±5.83* 12.02±8.96 54.23±10.14* 5.90±4.41*△
Low-dose JLSG-treated 10 27.63±6.54* 11.51±6.40 55.70±7.60* 4.47±3.20△
5-FU-treated 8 27.18±6.99 13.22±7.14 52.77±12.68* 6.76±3.98*△
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